cinnarizine and Migraine-Disorders

To investigate and analyze the available data on the prophylactic effectiveness of cinnarizine in migraine disorder.. Cinnarizine has demonstrated encouraging potential in preventing the attacks of migraine. Therefore, we opted to evaluate whether its sole administration leads to positive outcomes.. The PubMed, Scopus, Web of Science, and Embase databases were searched for English-only original interventional studies published until April 2022, then screened for relevancy and eligibility. The resulting data from the included studies, including the primary (ie, headache episode frequency, intensity, duration, monthly timing, and analgesic intake frequency) and secondary (ie, reported adverse events, quality of life, and activities of daily living) outcome changes compared to placebo and active controls (e.g., sodium valproate and propranolol) were then recorded by two independent assessors. Ultimately, these data were synthesized qualitatively and quantitatively (achieved by determining the mean difference via the random-effects model).. A total of 10 studies comprising seven randomized controlled trials and three quasi-experimental studies were included. Compared to placebo, cinnarizine demonstrated significant improvements in migraine episode frequency (Mean difference = -3.10; Confidence interval = [-3.33, -2.88]; p-value < 0.001; I. Cinnarizine can be considered a safe and effective medication for migraine prophylaxis. However, the relatively small sample size made reaching a definite conclusion impossible. Therefore, a higher number of randomized controlled trials are recommended to be taken place to clarify the situation further.

Topics: Activities of Daily Living; Cinnarizine; Humans; Migraine Disorders; Propranolol; Quality of Life; Valproic Acid

Despite the available prophylactic and acute drugs for migraine management, this disabling disorder remains undertreated especially among pediatrics. In this review, the authors aim at assessing the preventive role cinnarizine plays in treating migraine based on previously published studies.. Randomized clinical trials, randomized controlled trials, non-randomized open-label trials, and retrospective studies concerning cinnarizine in migraine prevention in children and adults were reviewed. Especial attention was given to the response rate, migraine characteristics, and tolerability.. The majority of reviewed trials demonstrated that cinnarizine is comparable to the conventional drugs used in migraine prophylaxis. However, most of the reviewed studies were limited by a non-controlled open-label design. Due to poor planning and possibility of high placebo responses, particularly in children and adolescents, the interpretation of open-label studies' results should be done cautiously. The evidence shows that cinnarizine's effectiveness was more promising in pediatric migraineurs and adults with migraine-associated vertigo such as vestibular migraine. Therefore, while the efficacy of cinnarizine cannot be dismissed, before reaching a definite conclusion on its effectiveness, it is necessary to do further high-quality RCTs among both children and adults.

Topics: Adult; Calcium Channel Blockers; Child; Cinnarizine; Humans; Migraine Disorders

Prophylactic therapy of Ménière's disease (MD) includes betahistine and calcium-blockers (the latter also useful for migraine prevention). The aim of our work was to assess the efficacy of combined therapy with cinnarizine and betahistine in MD subjects both with and without migraine and poorly responsive to betahistine alone. Fifty-two MD subjects were included who were poorly responsive to betahistine during 6 months of follow-up; 29 were migraineurs. Combined therapy was administered with betahistine 48 mg/day and cinnarizine 20 mg BID for 1 month, 20 mg/day for 2 weeks and 20 mg every 2 days for 2 more weeks, and then repeated. Results were collected over 6 months of follow-up. MD subjects with and without migraine demonstrated a decrease in both vertigo spells and migrainous attacks during combined therapy (from 9.4 to 3.8 and from 6.8 to 5.9 in 6 months, respectively, for vertigo spells, while migraine decreased from 3.8 to 1 in 6 months, respectively). A correlation was seen between decrease of vertigo spells and headaches in the sample of MD subjects with migraine. Our data support a proactive role for cinnarizine in preventing vertigo spells, especially in MD patients with migraine.. La betaistina e i calcio-antagonisti si sono dimostrati efficaci nella profilassi della Sindrome di Ménière; i calcio-antagonisti sono utilizzati anche nella prevenzione degli episodi di cefalea emicranica. Scopo del nostro lavoro è stato quello di stabilire l'efficacia della terapia combinata con cinnarizina e betaistina nella prevenzione delle crisi vertiginose in un gruppo di pazienti affetti da Sindrome di Ménière senza e con comorbidità per emicrania. Cinquantadue pazienti affetti da Sindrome di Ménière, poco responsivi alla sola terapia con betaistina in un periodo di 6 mesi, sono stati inclusi nello studio, 29 dei quali emicranici. Nei 6 mesi successivi è stata effettuata terapia combinata con betaistina (48 mg al giorno) e cinnarizina 20 mg due volte al giorno per 1 mese, 20 mg al giorno per 2 settimane e 20 mg a giorni alterni per 2 ulteriori settimane; lo schema terapeutico è stato indi ripetuto. I dati relativi alla frequenza delle crisi vertiginose sono stati collezionati nei 6 mesi successivi. In entrambi i gruppi è stato dimostrato un decremento delle crisi vertiginose (da 9.4 a 3.8 in 6 mesi e da 6.8 a 5.9 in 6 mesi rispettivamente nel gruppo con e senza comorbidità per emicrania; le crisi di cefalea si sono inoltre ridotte da 3.8 a 1 in 6 mesi). È stata evidenziata una correlazione tra la diminuzione degli attacchi di vertigine ed emicrania. I nostri dati sottolineano un ruolo terapeutico della cinnarizina nella prevenzione degli attacchi di vertigine soprattutto nei soggetti con comorbidità emicranica.

Topics: Betahistine; Calcium Channel Blockers; Cinnarizine; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Meniere Disease; Middle Aged; Migraine Disorders; Vertigo

Despite ongoing dispute over the pathophysiologic basis of migraine, the vasospastic theory of pathogenesis has brought to the forefront a promising class of new antimigraine agents, the Ca2+ channel antagonists. Voltage-dependent Ca2+ channels, integral membrane proteins that permit extracellular Ca2+ to enter cells down their electrical and concentration gradients, have a universal role in stimulus-response coupling in excitable cells. Thus, they participate in translating electrical excitation into secretory and contractile events. Ca2+ channel antagonists, a structurally diverse group of organic compounds, inhibit ion flux through voltage-dependent Ca2+ channels by binding to specific, channel-associated drug receptor sites and thereby reduce the frequency of channel opening in response to membrane depolarization. Ca2+ channels in cardiac muscle, smooth muscle, and neurons all exhibit high affinity for Ca2+ channel antagonists, although neurons also contain a population of drug-resistant channels. Extensive clinical experience in the use of Ca2+ channel antagonists has accumulated from their application to nonneurologic, especially cardiovascular, disorders. Three such drugs, nifedipine, verapamil, and diltiazem, are currently available in the United States, although none are specifically approved for use in migraine. Other agents, such as nimodipine, are likely to be released in the near future. A large number of clinical studies have now addressed the efficacy of Ca2+ channel antagonists in the prophylaxis of migraine headache. Dihydropyridines (nifedipine and nimodipine), phenylalkylamines (verapamil), diphenylalkylamines (flunarizine), and benzothiazepines (diltiazem) have all been examined, and a beneficial effect has been noted in each case. The limited directly comparative data currently available and the difficulties involved in comparing the results of different studies do not presently support claims of superiority for any single agent. This is an issue that will require attention as these drugs achieve more widespread use in migraine. Existing evidence suggests that flunarizine, verapamil, nifedipine, and nimodipine are effective prophylactic agents in both common and classic migraine. Nifedipine and nimodipine also appear to be valuable for the treatment of cluster headache. Two case reports describing favorable responses to flunarizine in childhood hemiplegic migraine are the only available data concerning the utility of these drugs in "c

Topics: Calcium; Calcium Channel Blockers; Cinnarizine; Diltiazem; Flunarizine; Humans; Ion Channels; Kinetics; Migraine Disorders; Nicotinic Acids; Nifedipine; Nimodipine; Verapamil

According to classic theory, a migraine attack is initiated by cerebrovascular spasm followed by extracranial vasodilatation. Results of recent studies support this theory and suggest that cerebral blood flow during the initial phase of migraine symptoms is, in fact, decreased and this decrease probably leads to ischemia and hypoxia. Cellular hypoxia, in turn, can cause an increase in the flow of calcium from the extracellular fluid to the intracellular space, resulting in calcium overload and cellular dysfunction. Because calcium-channel blockers selectively inhibit the intracellular influx of calcium ions, investigators have begun evaluating the efficacy of these agents for migraine prophylaxis. Nimodipine, a calcium-channel blocker that exhibits selective effects on cerebral vessels, seems to offer protection against the cerebral ischemia and hypoxia presumed to be operative during migraine attacks. In a double-blind, placebo-controlled study, nimodipine decreased the frequency and duration of migraine attacks by at least half in 69% of patients treated with this agent. Comparable reductions in migraine frequency and duration were attained in 58, 51, 41 and 52% of patients treated with methysergide maleate, pizotifen, clonidine hydrochloride and propranolol, respectively. The piperazine derivative flunarizine also has calcium-channel blocking properties. This agent prevents vasospasm in cerebral arteries and protects against cerebral hypoxia. Results of double-blind studies of migraine prophylaxis with flunarizine demonstrate the beneficial effects of this agent, particularly in younger patients. Flunarizine proved to be superior to pizotifen in decreasing the severity of migraine attacks and comparable to pizotifen in decreasing their frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Calcium Channel Blockers; Cinnarizine; Double-Blind Method; Flunarizine; Humans; Hypoxia; Migraine Disorders; Nicotinic Acids; Nimodipine; Vasodilator Agents

Topics: Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Diltiazem; Double-Blind Method; Flunarizine; Humans; Migraine Disorders; Nicotinic Acids; Nifedipine; Nimodipine; Verapamil

Flunarizine is a 'selective' calcium entry blocker with a similar chemical structure and pharmacological profile to the related compound, cinnarizine. However, in contrast to cinnarizine it has a long plasma half-life and need only be given once a day. The majority of therapeutic trials in the prophylaxis of migraine, occlusive peripheral vascular disease and vertigo of central or peripheral origin have been placebo-controlled, and have shown that the drug produces significantly greater beneficial effects than placebo as evaluated by subjective and objective criteria. A small number of comparative studies have shown flunarizine to be at least as effective as pizotifen in migraine prophylaxis, and in a longer term study as effective as cinnarizine in vertigo of central origin. However, it has not been compared with other drugs which may be useful in these areas, such as methysergide in migraine prophylaxis, some antihistamines or phenothiazines in vertigo, or (understandably at this stage of its evolution) with surgical revascularisation in severe occlusive peripheral vascular disease. In preliminary placebo-controlled studies there was some evidence that flunarizine may improve impaired cognitive function in patients with cerebrovascular disorders, but such findings need further confirmation in additional carefully conducted studies. With a very long half-life, flunarizine may be given once daily; and drowsiness, the main side effect, can be minimised by taking the daily dose in the evening. Thus, it appears that flunarizine will offer a useful alternative in some therapeutic areas that can be difficult to manage with previously available therapy. However, a definitive statement on its relative place in therapy of such conditions must await a few well-controlled comparative studies.

Topics: Adult; Age Factors; Aged; Animals; Anti-Arrhythmia Agents; Anticonvulsants; Blood; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Flunarizine; Histamine H1 Antagonists; Humans; Kinetics; Migraine Disorders; Piperazines; Vascular Diseases; Vasodilator Agents; Vertigo

Topics: Adult; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Female; Flunarizine; Humans; Male; Migraine Disorders; Piperazines; Pizotyline; Time Factors

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Analgesics; Antidepressive Agents, Tricyclic; Cinnarizine; Clonidine; Drug Evaluation; Drug Synergism; Drug Therapy, Combination; Ergotamine; Humans; Kinins; Middle Aged; Migraine Disorders; Serotonin Antagonists

Acute migraine attacks disrupt performance and reduce the quality of life. Therefore, efforts to prevent these attacks continue using different medications. This study aimed to compare the effect of cinnarizine combination with propranolol and propranolol with placebo in preventing acute migraine attacks. This study was a semi-experimental study performed on 120 adult patients with migraine referred to Department of Neurology in Rezgary Teaching Hospital in Erbil.. Participants were randomly allocated to two groups control (propranolol) and intervention (propranolol with cinnarizine). The frequency, duration and severity of headache attacks were recorded and followed within two months. Data were analyzed with SPSS ver23 software and T-paired, independent T-tests and ANOVA. The average age of the participants was 34.54 years. 60% were female and 55% had a family history of migraine. The average frequency of headache attacks in the intervention group decreased by 75 % (from 15 times to 3 times) and a 50 % decrease in the control group (from 12 times to 6 times). The duration and severity of headaches in both intervention and control groups decreased (p <0.001), respectively. The average frequency, duration and severity of headache attacks in the first- and second months during treatment in the intervention group and control group were statistically different (p <0.001). The drug combination of propranolol with cinnarizine has an additional effect on reducing acute migraine attacks compared to propranolol alone.

Topics: Adult; Cinnarizine; Female; Headache; Humans; Male; Migraine Disorders; Propranolol; Quality of Life

Few migraine preventive agents have been assessed in a pediatric population. We evaluated the safety and efficacy of cinnarizine and sodium valproate for migraine prophylaxis in children and adolescents.. We carried out a randomized double-blind placebo-controlled trial in the Children's Medical Center and Sina hospital, Tehran, Iran. Eligible participants were randomly assigned in 1:1:1 ratio via interactive web response system to receive either cinnarizine, sodium valproate, or placebo. The primary endpoints were the mean change in frequency and intensity of migraine attacks from baseline to the last 4 weeks of trial. The secondary endpoint was the efficacy of each drug in the prevention of migraine. The drug was considered effective if it decreased migraine frequency by more than 50% in the double-blind phase compared with the baseline. Safety endpoint was adverse effects that were reported by children or their parents.. A total of 158 children participated. The frequency of migraine attacks significantly reduced compared to baseline in cinnarizine (difference: -8.0; 95% confidence interval (CI): -9.3 to -6.6), sodium valproate (difference: -8.3; 95% confidence interval: -9.3 to -7.2), and placebo (difference: -4.4; 95% confidence interval: -5.4 to -3.4) arms. The decrease was statistically greater in cinnarizine (difference: -3.6; 95% confidence interval: -5.5 to -1.6) and sodium valproate (difference: -3.9; 95% confidence interval: -5.8 to -1.9) arms, compared to placebo group. Children in all groups had significant reduction in intensity of episodes compared to baseline (cinnarizine: -4.6; 95% confidence interval: -5.2 to -4.0; sodium valproate: -4.0; 95% confidence interval: -4.8 to -3.3; placebo: -2.6; 95% confidence interval: -3.4 to -1.8). The decrease was statistically greater in cinnarizine (difference: -2.0; 95% confidence interval: -3.2 to -0.8) and sodium valproate (difference: -1.5; 95% confidence interval: -2.7 to -0.3) arms, compared to the placebo group. Seventy-one percent of individuals in the cinnarizine group, 66% of cases in the sodium valproate group, and 42% of people in the placebo arm reported more than 50% reduction in episodes at the end of the trial. The odds ratio for >50% responder rate was 3.5 (98.3% confidence interval: 1.3 to 9.3) for cinnarizine versus placebo and 2.7 (98.3% confidence interval: 1.0 to 6.9) for sodium valproate versus placebo. Nine individuals reported adverse effects (three in cinnarizine, five in sodium valproate, and one in the placebo group) and one case in the sodium valproate group discontinued the therapy due to severe sedation.. Cinnarizine and sodium valproate could be useful in migraine prophylaxis in children and adolescents.

Topics: Adolescent; Calcium Channel Blockers; Child; Cinnarizine; Double-Blind Method; Female; GABA Agents; Humans; Iran; Male; Migraine Disorders; Valproic Acid

In spite of the high occurrence of migraine headaches in school-age children, there are currently no approved and widely accepted pharmacologic agents for migraine prophylaxis in children. Our previous open-label study in children revealed the efficacy of cinnarizine, a calcium channel blocker, in migraine prophylaxis. A placebo-controlled trial was conducted to demonstrate the efficacy and safety of cinnarizine in the prophylaxis of migraine in children.. A double-blind, placebo-controlled, parallel-group study conducted in a tertiary medical center in Tehran, Iran.. Children (5-17 years) who experienced migraines with and without aura, as defined on the basis of 2004 International Headache Society criteria, were recruited into the study. Children were excluded if they had complicated migraine, epilepsy, or a history of use of migraine prophylactic agents. Each participant was randomly assigned to receive cinnarizine (a single 1.5 mg/kg/day dose in children weighing less than 30 kg and a single 50 mg dose in children weighing more than 30 kg, administered at bedtime) or placebo. The frequency, severity, and duration of headaches over the trial period were assessed and adverse effects were monitored.. A total of 68 children (34 in each group) with migraine were enrolled and 62 participants completed the study. After 3 months of taking cinnarizine or placebo, children in both groups experienced significantly reduced frequency, severity, and duration of headaches compared with baseline measurements (P < 0.001). However, compared with 31.3% of children in the placebo group, 60% of children in the cinnarizine group reported more than 50% reduction in monthly headache frequency (P = 0.023), suggesting that cinnarizine was significantly more effective than placebo in reducing the frequency of headaches. No serious adverse effects of the medications were observed in the treated children, including no abnormal weight gain or extrapyramidal signs.. Our results indicate that the use of cinnarizine at doses administered in this study is effective and safe for prophylaxis of migraine headaches in children.

Topics: Adolescent; Calcium Channel Blockers; Child; Child, Preschool; Cinnarizine; Double-Blind Method; Female; Humans; Male; Migraine Disorders; Treatment Outcome

The aim of this randomized, double-blind, parallel-group study was to compare the efficacy and safety of low-dose cinnarizine and sodium valproate in migraine prophylaxis.. A total of 104 patients were treated during a 12-week treatment period. Cinnarizine dose of 25 mg and 200-mg sodium valproate were administered every 12 hours. During follow-up period, frequency, intensity and duration of migraine attacks, symptoms associated with headache, analgesics use, as well as drugs' side effects were studied. Participants completed Migraine Disability Assessment (MIDAS) and Headache Impact Test (HIT-6) questionnaires before and after treatment.. Frequency, intensity and duration of migraine headaches as well as MIDAS score and administration of symptomatic medications decreased significantly between repeated follow-up visits in both groups. Reduction of 4-week migraine frequencies in patients receiving cinnarizine and valproate was 36.4% and 55%, respectively, and the difference between two groups was statistically significant (p < 0.001).. Our results showed that administration of 25-mg cinnarizine every 12 hours can significantly decrease headache duration (p ≤ 0.001) and headache frequency (p ≤ 0.001) in patients with migraine. These results suggest that cinnarizine may be an appropriate substitution for first-line migraine prophylaxis such as valproate.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Calcium Channel Blockers; Cinnarizine; Double-Blind Method; Female; Humans; Male; Middle Aged; Migraine Disorders; Valproic Acid

Migraine headaches are common in children. Early diagnosis and appropriate interventions are mandatory to prevent decades of suffering and diminished quality of life. There is need for data regarding the efficacy and safety of prophylactic agents in children with migraine; therefore, we designed a randomized clinical trial to compare the efficacy and safety of cinnarizine with that of a well-known prophylactic agent (propranolol) in the prophylaxis of pediatric migraine headache. A total of 120 patients aged between 6 and 17 years were recruited and 113 patients succeeded in completing all phases of the trial. Of them, 57 patients were given cinnarizine, and propranolol was administered in 56 patients. Reduction in headache frequency was the main response to treatment. Cinnarizine reduced the baseline headache frequency by more than 50% in 74.6% of patients and the mean headache frequency per month was reduced from 11.851 ± 0.739 (mean ± SEM) to 3.358 ± 0.739 (mean ± SEM) attacks per month (P < 0.001). In the propranolol group, more than 50% reduction of the baseline headache frequency was seen in 72.5% of patients and the mean headache frequency per month was reduced from 10.264 ± 0.830 (mean ± SEM) to 2.774 ± 0.830 (mean ± SEM) attacks per month (P < 0.001). No significant difference was seen in 50% reduction of the baseline headache frequency between treatment groups (P = 0.358). No significant adverse effects were reported. In this open study, cinnarizine appeared thus as effective as propranolol and safe for the prophylaxis of migraine in children, but this remains to be confirmed in a double-blind placebo-controlled trial.

Topics: Adolescent; Analysis of Variance; Calcium Channel Blockers; Chi-Square Distribution; Child; Cinnarizine; Female; Humans; Male; Migraine Disorders; Propranolol; Quality of Life; Retrospective Studies; Treatment Outcome; Vasodilator Agents

This was a double-blind clinical trial designed to assess the efficacy and safety of the cinnarizine (CIN) in patients with migraine who were refractory to propranolol and tricyclic antidepressants in comparison with sodium valproate (SV) to investigate whether CIN could be at least as effective as SV. A total of 125 patients were treated in a treatment period of 12 weeks. All patients had at least one intake of trial medication and 2-week post baseline efficacy observation which all were included in the ITT analysis. Of the 125 subjects treated, 46 discontinued prematurely: 25 from the CIN and 21 from the SV group. The main reasons for premature discontinuation were: lost to follow up (25/46, 63.2%), insufficient response (16/46, 20%), and adverse events (5/46, 12.8%). No statistically significant inter-group differences in the number of discontinuation was observed (p > 0.05). In both groups, number of attacks, intensity, and duration of attacks significantly decreased (p < 0.05). No statistically significant inter-group differences were observed regarding the mean number of attacks, duration, and intensity of migraine attacks for any of the time intervals analysed, except for the mean reduction of third and fourth visits intensity from baseline which were significantly different in two groups (p < 0.05), with the CIN group showing more reduction. Analysis of the number of responders showed that in the CIN group 61.2% subjects were responders, and 63.8% in the SV group. No statistically significant differences between the treatment groups were found for any of the secondary parameters. Overall 26 subjects reported one or more adverse events during the study period: 13 subjects in each group. Five subjects discontinued prematurely due to adverse events; two in the CIN group with significant weight gain, and 3 in the SV group with significant weight gain and severe tremor. These results suggest that CIN is an effective and safe prophylactic agent even in severe migraine headache.

Topics: Adolescent; Adult; Calcium Channel Blockers; Cinnarizine; Female; GABA Agents; Humans; Male; Middle Aged; Migraine Disorders; Treatment Outcome; Valproic Acid

Headache and vertigo often emerge simultaneously. Fifty six (40%) out of 140 patients complaining of vertigo were studied. Emerging in the aura and/or in headache phases, vertigo was more frequently registered in patients suffered from migraine with aura (57%). Vertigo associated with migraine was diagnosed in 25% of the cases. The patients were randomized into 2 equal identical groups, one of which was treated by betaserc (16 mg, 3 times daily before meal) and the other one was given cinnarizine (25 mg, 3 times daily). Treatment duration was 12 weeks. Reduction of vertigo attacks frequency and headache by 50% and over, in comparison to the baseline period, was considered as beneficial. Fifty three (95%) patients completed the treatment course. Decrease of a risk for negative results and a frequency of positive effect of vertigo therapy were significantly higher in the group receiving betaserc. Reduction of monthly relapses by 50% and over was detected in 79% of the patients of betaserc group and in 52% of those of cinnarizine one. Migraine attacks monthly frequency was diminished by 43% and 64%, respectively. Therefore, betaserc is considered for using as vertigolytic medication and for migraine attacks prevention.

Topics: Adult; Analysis of Variance; Betahistine; Cinnarizine; Female; Histamine Agents; Humans; Male; Middle Aged; Migraine Disorders; Treatment Outcome; Vertigo

Some of the so-called calcium antagonists are effectively applied in the prophylactic treatment of migraine. Magnesium compounds reveal some calcium- antagonistic features, which was the reason of magnesium compounds (magnesium sulphate i.m. or magnesium lactate p.o.) evaluation at chronic migraine-patients. The compounds were administered or alone or in combination with cinnarizine (in case of magnesium sulphate). Beneficial effects were registered both after application of magnesium sulphate and, more markedly, after the combination with cinnarizine. The potentiation of the effect is likely due, at least partially, to their own calcium-antagonistic features. The side-effects of the applied drugs were not registered.

Topics: Adult; Cinnarizine; Drug Therapy, Combination; Female; Headache; Humans; Magnesium Sulfate; Male; Migraine Disorders

Topics: Administration, Oral; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Ergotamine; Ergotamines; Female; Flunarizine; Humans; Male; Migraine Disorders; Random Allocation

Topics: Adult; Body Weight; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Pizotyline; Random Allocation; Thiophenes

The results of a double-blind cross-over clinical trial involving 27 patients with classical or common migraine are described to compare the prophylactic effect of the calcium entry blocker flunarizine with that of pizotifen. Duration of the treatment was two months, with an evening single-dose administration of both drugs. For most parameters, there was no definite difference between flunarizine and pizotifen in migraine prophylaxis. It has been demonstrated previously that pizotifen is an effective drug in migraine prophylaxis, and these results suggest that flunarizine is effective, too. Weight gain as a side effect was less frequent and less severe with flunarizine than with pizotifen; other side effects showed the same incidence with both drugs.

Topics: Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Flunarizine; Humans; Migraine Disorders; Pizotyline; Thiophenes; Time Factors

After four weeks of medication-free baseline observation, 29 patients with common migraine randomly received flunarizine (10 mg daily) or placebo for a 16-week period. After four weeks wash-out they crossed treatments for another 16 weeks; 27 patients completed the trial. Compared with placebo, flunarizine significantly reduced the frequency of migraine attacks and the derived headache indices, but the duration and severity of single attacks remained unchanged (Mann-Whitney U-test). The effect of flunarizine increased during the 16-week treatment period and during the last four weeks the number of migraine attacks reduced to 50% compared to the wash-out period. The only side-effect of flunarizine was mild daytime sedation in three patients. It is concluded that flunarizine is a valuable new prophylactic agent for common migraine.

Topics: Adolescent; Adult; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Random Allocation; Time Factors; Vasodilator Agents

In this double-blind study versus placebo, the anti-migraine efficacy of flunarizine 20 mg/per os/day for 14 days, followed by 10 mg/per os/day up to 120 days has been evaluated in 30 patients suffering from common and classical migraine. During the trial the vestibular function (slow phase velocity (SPV) and number of spikes) was also studied. To date 18 patients have completed the study. The results show a significant difference before and after the treatment with flunarizine, while no difference was observed in the placebo group, with regard to headache unit indices. Flunarizine seems to increase SPV max, which is reduced between attacks in migraine patients; the number of spikes does not change significantly.

Topics: Adolescent; Adult; Cinnarizine; Electronystagmography; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders

Pharmacological data and early clinical experience have suggested that the calcium entry blocker flunarizine may be a valuable gain in the prophylaxis of migraine. This was supported by a study in 20 patients with classical migraine who were, after a drug free run-in phase, orally treated with either placebo or flunarizine (10 mg at night) for 3 to 4 months. Flunarizine significantly reduced the frequency, duration and severity of the migraine attacks. A corrected migraine index, based on these 3 variables was reduced by 82% in the drug group but increased by 66% in the control patients. Only 1 patient did not clearly benefit from flunarizine. In some cases flunarizine should be administered for at least 4 months before judging its efficacy. No side-effects occurred.

Topics: Adult; Aged; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Piperazines; Placebos

Pharmacological data and early clinical experience have suggested that the calcium entry blocker flunarizine may be a valuable asset in the prophylaxis of migraine. This was supported by a study in twenty patients with classical migraine who were, after a drug-free running-in phase, orally treated with either placebo or flunarizine (10 mg at night) for three to four months. Flunarizine significantly reduced the frequency, duration and severity of the migraine attacks. A corrected migraine index, based on these three variables, was reduced by 82% in the drug group but increased by 66% in the control patients. Only one patient did not clearly benefit from flunarizine, and the response in another illustrated that flunarizine has to be given for at least four months before its efficacy can be judged in some cases. No side effects occurred.

Topics: Adult; Aged; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Piperazines; Random Allocation

Flunarizine was given in daily doses of 10 mg for periods of two to four months to 176 patients suffering from various types of headache. The symptoms were improved in 82% of the cases treated. No differences emerged among the various types of headache reported by the patients or in relation to the presence or absence of neurological involvement or its type.

Topics: Adolescent; Adult; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Female; Flunarizine; Headache; Humans; Male; Middle Aged; Migraine Disorders; Piperazines; Vascular Headaches

In order to assess the effects of flunarizine in long-term prophylaxis of common migraine, 120 subjects (90 female and 30 male) were treated with 10 mg at bedtime and followed-up for two years. The effectiveness of the drug was assessed by investigating the variations of the Headache Index (HI) and of the intake of analgesics. The patients considered responders were those with an at least 60% reduction of the HI compared with the baseline value. To assess side effects, on each follow-up examination the patients were weighed and submitted to the Hamilton Rating Scale for Depression, Toulouse-Pieron test for attention, and arousal test. By the third month of therapy, the average monthly HI had decreased from a baseline value of 16.5 +/- 7.0 to 7.5 +/- 4.2. Also by the third month, 60 subjects had proved responders and 50 non-responders; 10 had dropped out of the study because of side effects or for other reasons. The only statistically significant differences between responders and non-responders were in the baseline HI, which was higher among responders, and in the baseline intake of analgesics, which was higher in non-responders.

Topics: Adolescent; Adult; Body Weight; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Female; Flunarizine; Follow-Up Studies; Humans; Male; Middle Aged; Migraine Disorders; Patient Compliance; Piperazines

Topics: Adult; Blood Pressure; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Female; Flunarizine; Heart Rate; Humans; Male; Middle Aged; Migraine Disorders; Piperazines

The effects of flunarizine administration (10 mg/day, at bed time) were studied in 120 common migraine patients who were followed for 24 months with quarterly controls. Besides headache index (HI) and analgesic use, other variables were monitored, such as arousal (Tolouse Pieron test), mood (Hamilton rating scale for depression), sleep/wake (hrs) and body weight. The study was open-type and after the 6th month control some responder (R) cases (HI reduction greater than or equal to 60%) presenting HI scores less than or equal to 4 could continue the survey off-treatment. The percentage of R cases was 54.5% at the 3rd month, a figure that further increased up to 72% by the 9th month; relapses on treatment were not observed and rebound-headache occurred in 1/4 of R cases let off-treatment. Lower (p less than 0.05) baseline HI values characterized non-responders. Side-effects not requiring withdrawal were drowsiness (42% within the 1st month) and weight gain (mean 7.9 +/- 6.9 kg) in 54% of the cases, while a retarded type depression was the most frequent cause of drop-out from trial (7.5%). The results, while confirming the high prophylactic activity of flunarizine in common migraine, stress the importance of clinical long-term survey of side-effects using antimigraine drugs and suggest the need for further investigations about flunarizine effects on CNS.

Topics: Adolescent; Adult; Body Weight; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Depression; Female; Flunarizine; Follow-Up Studies; Humans; Male; Middle Aged; Migraine Disorders; Piperazines; Sleep Stages

Topics: Adolescent; Adult; Aged; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Piperazines; Pizotyline

Topics: Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Diltiazem; Double-Blind Method; Flunarizine; Humans; Migraine Disorders; Nicotinic Acids; Nifedipine; Nimodipine; Verapamil

Flunarizine, a slow-channel calcium blocker, appeared to be effective in the prophylactic treatment of common and classic migraine in 29 out-patients included in a double-blind clinical trial. After a two-month placebo period, half the patients were treated with flunarizine, 10 mg a day for up to 120 days, half with placebo. Electronystagmographic (ENG) recordings were performed at the end of the common placebo period and after two and four months of treatment, respectively. There was a significant reduction in Headache Unit Index (HUI) and Headache Unit Index Corrected (HUIC) (42% and 40.5% respectively) in the flunarizine-treated group but not in the placebo group. Analgesic intake was reduced and intensity of pain was unchanged in both groups throughout the trial. ENG data were not significantly affected by flunarizine treatment.

Topics: Adult; Cinnarizine; Electronystagmography; Eye Movements; Female; Flunarizine; Humans; Male; Migraine Disorders; Piperazines; Vestibular Function Tests

Flunarizine, a Ca-antagonist with demonstrated antimigraine properties, and indoprofen, an anti-inflammatory non-steroidal agent, were used in the treatment of daily chronic headache. Forty-two migraineurs with interval headache (MIH) were treated with flunarizine in a 6-month open trial, while indoprofen was administered to 23 patients with MIH and 7 with chronic tension headache (CTH) in a 2-month, double-blind, cross-over placebo-controlled study. Flunarizine was found effective in over 65% of the patients, while indoprofen was able to improve headache severity in only 30% of the subjects. In the responder patients, the effectiveness of both drugs is more pronounced in MIH, and seems to be ascribable to the ability of the treatments to reduce number and severity of attacks. A higher incidence of previous affective disturbances is found in non-responsive cases. The analysis of factors converting episodic into chronic headache shows slight but not significant differences between responders and non-responders. An impairment of plasma beta-endorphin levels, in the presence of normal ACTH, cortisol and nociceptive RIII threshold values, characterizes daily chronic headache (DCH) patients. Moreover, indoprofen does not significantly affect these biological and neurophysiological parameters independently of the therapeutic response.

Topics: Adult; Anti-Inflammatory Agents; Calcium Channel Blockers; Cinnarizine; Endorphins; Female; Flunarizine; Headache; Humans; Indoprofen; Male; Migraine Disorders; Pain; Phenylpropionates; Piperazines; Sensory Thresholds

Flunarizine is a 'selective' calcium entry blocker with a similar chemical structure and pharmacological profile to the related compound, cinnarizine. However, in contrast to cinnarizine it has a long plasma half-life and need only be given once a day. The majority of therapeutic trials in the prophylaxis of migraine, occlusive peripheral vascular disease and vertigo of central or peripheral origin have been placebo-controlled, and have shown that the drug produces significantly greater beneficial effects than placebo as evaluated by subjective and objective criteria. A small number of comparative studies have shown flunarizine to be at least as effective as pizotifen in migraine prophylaxis, and in a longer term study as effective as cinnarizine in vertigo of central origin. However, it has not been compared with other drugs which may be useful in these areas, such as methysergide in migraine prophylaxis, some antihistamines or phenothiazines in vertigo, or (understandably at this stage of its evolution) with surgical revascularisation in severe occlusive peripheral vascular disease. In preliminary placebo-controlled studies there was some evidence that flunarizine may improve impaired cognitive function in patients with cerebrovascular disorders, but such findings need further confirmation in additional carefully conducted studies. With a very long half-life, flunarizine may be given once daily; and drowsiness, the main side effect, can be minimised by taking the daily dose in the evening. Thus, it appears that flunarizine will offer a useful alternative in some therapeutic areas that can be difficult to manage with previously available therapy. However, a definitive statement on its relative place in therapy of such conditions must await a few well-controlled comparative studies.

Topics: Adult; Age Factors; Aged; Animals; Anti-Arrhythmia Agents; Anticonvulsants; Blood; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Flunarizine; Histamine H1 Antagonists; Humans; Kinetics; Migraine Disorders; Piperazines; Vascular Diseases; Vasodilator Agents; Vertigo

Seventeen patients with common or classic migraine were prophylactically treated with 10 mg flunarizine daily, whereas 18 patients received a placebo during a 12-week randomized double-blind study. In the gross flunarizine was significantly superior to the placebo. Only 3 patients felt that flunarizine had been useless and the investigator also guessed the medication code correctly in all but these 3 cases. After a 1-month starting period the difference between flunarizine and placebo in reducing the frequency of the migraine attacks became statistically significant in favour of flunarizine. The mean monthly number of attacks was respectively 3.3 and 3.8 before the study and 1.4 and 3.2 during the study. The limited scale of the trial precluded a judgment as to whether one type of migraine would respond better to flunarizine than the other. Side-effects were negligible, weight gain being secondary to the therapeutic effect rather than an untoward consequence of treatment.

Topics: Adult; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Piperazines; Random Allocation

Seventeen patients with common or classical migraine were prophylactically treated with 10 mg flunarizine daily whereas 18 patients received a placebo during a 3-month randomized double-blind study. Globally, flunarizine was significantly superior to the placebo. Only three patients felt that flunarizine had been useless and the investigator also guessed the medication code correctly in all but these three cases. Beyond a 1-month starting period the frequency of the migraine attacks became significantly lower with flunarizine than with the placebo. The mean monthly number of attacks was respectively 3.3 and 3.8 before the study and 1.4 and 3.2 during the study. The limited scale of the trial precludes a judgment as to whether one type of migraine would respond better to flunarizine than the other. Side-effects were negligible, weight gain being considered rather a secondary gain than an untoward consequence of treatment.

Topics: Body Weight; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Flunarizine; Humans; Migraine Disorders; Piperazines; Vasodilator Agents

Topics: Adult; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Female; Flunarizine; Humans; Male; Migraine Disorders; Piperazines; Pizotyline; Time Factors

In this double-blind, randomized multicenter study involving 75 patients, the calcium-entry blocker flunarizine (10 mg nocte) was compared with pizotifen (2-3 mg per day in three administrations). Duration of treatment was four months. The results suggest that, in the dosage used, flunarizine is at least as effective as pizotifen in both classical and common migraine as regards effect on attack frequency. Flunarizine might tend to more markedly suppress severity of the attack, though. The weight gain seen with both drugs might be slightly less with flunarizine. A practical advantage of flunarizine is its simple dosage schedule (one intake per day).

Topics: Adolescent; Adult; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Piperazines; Pizotyline; Random Allocation; Thiophenes

Topics: Animals; Chickens; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Flunarizine; Hypoxia, Brain; Migraine Disorders; Models, Biological; Piperazines; Placebos; Rodentia

Topics: Adult; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Piperazines; Sex Factors; Time Factors; Vasodilator Agents

Topics: Cinnarizine; Female; Flunarizine; Histamine H1 Antagonists; Humans; Male; Migraine Disorders; Piperazines

According to Pearson's method (correlation coefficient) the group of improved patients is 16.88% of the expected total result (frequency of attacks regressed to 50%, 25% or 0%): for cyproheptadine, pizotifene, methysergide, methergoline, histamine, clonidine, allylpropylmalonyl urea 'p' is less than 0.001, for cinnarizine less than 0.02. For hemicrania we used cinnarizine, cyproheptadine, clonidine, histamine, pizotifene and reserpine; for cluster headache, cinnarizine, cyproheptadine, clonidine, histamine and reserpine; for tension headache, cyproheptadine; for psychogenic headache, allylpropylmalonylurea. In attacks of hemicrania or paroxysmal crises with undulant headache or persistent headache, positive statistically significant results were obtained with a combination of indomethacin, prochlorperazine and caffeine.

Topics: Aspirin; Caffeine; Cinnarizine; Clinical Trials as Topic; Clonidine; Cyproheptadine; Drug Therapy, Combination; Ergotamine; Headache; Histamine; Humans; Indomethacin; Metergoline; Methysergide; Migraine Disorders; Pizotyline; Prochlorperazine; Reserpine; Retrospective Studies; Urea

Topics: Calcium Channel Blockers; Cinnarizine; Flunarizine; Humans; Migraine Disorders; Piperazines; Terminology as Topic

Topics: Child; Cinnarizine; Double-Blind Method; Humans; Migraine Disorders; Propranolol; Valproic Acid

Topics: Adolescent; Child; Cinnarizine; Double-Blind Method; Humans; Migraine Disorders; Valproic Acid

Vestibular migraine (VM) is one of the most frequent causes of episodic vertigo, with a lifetime prevalence of 0.98%. Prophylactic therapy includes calcium channel blockers, beta-blockers, antiepileptic drugs and antidepressants. We studied the association of cinnarizine 20 mg and dimenhydrinate 40 mg (Arlevertan) in a group of 22 patients affected by definite VM. Proposed therapy included one tablet twice a day for 1 month, which was repeated three times with 1 month of interval between drug intake; results were compared with those of a control group of 11 VM patients who asked to observe only lifestyle measures for migraine. The main outcome was the number of vertigo and headache crises in the 6 months before therapy and in the 6 months of follow-up. Subjects performing Arlevertan presented during the 6 months of therapy a decrease of vertigo attacks from 5.3 to 2.1 and of headaches from 4.3 to 1.7 (p < 0.0001); 68% of these subjects reported a decrease of at least 50% of vertigo attacks, while 63% of headaches. Conversely, vertigo attacks decreased from 3.5 to 2.2 and headaches from 2.6 to 2 in patients observing only lifestyle; 18% of these subjects reported a decrease of at least 50% of vertigo crises and 27% of headaches. Our data do not differ from those of previous works assessing efficacy of different prophylactic therapies for VM and reporting consistent reduction of vertigo spells in a rate of patients ranging from 60 and 80%.

Topics: Adult; Calcium Channel Blockers; Cinnarizine; Dimenhydrinate; Drug Combinations; Female; Follow-Up Studies; Histamine H1 Antagonists; Humans; Male; Migraine Disorders; Time Factors; Treatment Outcome; Vertigo; Vestibular Diseases

Topics: Adolescent; Calcium Channel Blockers; Child; Cinnarizine; Humans; Migraine Disorders

To assess the effectiveness and safety of cinnarizine as a migraine-preventive therapy.. Sixty patients with more than 2 migraine headache attacks during a 4-week baseline entered the study and received a 25-mg tablet cinnarizine twice daily for the first 3 days and then 3 times daily. They were assessed on weeks 2, 6, 10, and 14. Reduction from baseline in 4-week migraine headache rate was the primary efficacy variable. Reduction in migraine attacks duration and severity was also evaluated.. The mean reduction in 4-week migraine headache rate was 4.6 +/- 2.2 from the baseline of 6.2 +/- 2.2 after 14 weeks of treatment, which was statistically significant (P < 0.001). Percent reduction in 4-week migraine frequency was 35% after 2 weeks, 74% after 6 weeks, 74% after 10 weeks, and 75% after 14 weeks of treatment. Significant reduction in attack duration (P < 0.001) and severity (P < 0.001) was also noted. No serious adverse events were observed in this series of patient.. Cinnarizine is an efficacious and well-tolerated prophylactic antimigraine medication, which has early onset effectiveness.

Topics: Adolescent; Adult; Calcium Channel Blockers; Cinnarizine; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Migraine Disorders

Flunarizine and cinnarizine (IC50 6.8x10(-6) and 2.8x10(-5) M, respectively) inhibited 3H-serotonin uptake by platelets. In higher doses, they blocked serotonin-induced platelet aggregation and stimulated 3H-serotonin release from these cells. Imipramine did not affect serotonin-releasing effects of preparations. In all patients cinnarizine was more potent in inhibiting serotonin uptake, and in half of the patients cinnarizine displayed higher activity as an inductor of serotonin release.

Topics: Biological Transport; Calcium Channel Blockers; Cinnarizine; Flunarizine; Humans; Male; Migraine Disorders; Platelet Aggregation; Serotonin

Topics: Adrenergic beta-Antagonists; Amitriptyline; Aspirin; Benzoxepins; Calcium Channel Blockers; Cinnarizine; Clonidine; Dihydroergotamine; Flunarizine; Humans; Methysergide; Migraine Disorders; Pizotyline; Propranolol

Topics: Adolescent; Adult; beta-Thromboglobulin; Blood Platelets; Cinnarizine; Female; Flunarizine; Humans; Male; Migraine Disorders; Platelet Factor 4; Platelet Function Tests

Topics: Adrenergic beta-Antagonists; Anti-Anxiety Agents; Cinnarizine; Dihydroergotamine; Dose-Response Relationship, Drug; Flunarizine; Humans; Hypotension; Migraine Disorders; Time Factors

In order to study the role of platelets in migraine and cerebrovascular disease, beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) plasma levels, indices of in vivo platelet activation, were assayed in two groups of patients suffering from migraine (common/classic and classic/complicated migraine, respectively) and in one group suffering from transitory ischemic attacks (TIAs). Plasma determinations were carried out in the absence of treatment and during the administration of aspirin (50 mg/daily) and flunarizine (10 mg/daily). Platelet activation was found in patients suffering from TIA; patients affected by classic and complicated migraine showed a high incidence of activation, in comparison with common migraine sufferers, also in headache-free periods. Administration of aspirin (ASA) was more effective than flunarizine in inducing a decrease in beta-TG and PF4 plasma levels in migraineurs. Aspirin, however, did not affect platelet activation in subjects suffering from ischemic attack even though we did not observe any relapse after one year of treatment. The different effect of ASA in TIAs and migraine indicates that the platelet activation in TIA patients is due not only to cyclo-oxygenase pathway but also to other in vivo pathways.

Topics: Adult; Aged; Aspirin; beta-Thromboglobulin; Cinnarizine; Female; Flunarizine; Humans; Ischemic Attack, Transient; Male; Middle Aged; Migraine Disorders; Piperazines; Platelet Aggregation; Platelet Factor 4; Vasodilator Agents

Flunarizine (10 mg/day for 60 days) was given to eight postmenopausal women with common migraine. Plasma LH pulsatility fluctuation, peripheral concentrations of prolactin (PRL), cortisol, beta-endorphin (beta-EP), beta-lipotropin (beta-LPH) and Pain Total Index (PTI) were evaluated before and after treatment. PTI was significantly reduced by flunarizine, which did not affect beta-LPH, beta-EP and cortisol plasma levels. On the contrary, both PRL values and amplitude, and length of LH pulses had increased at the end of treatment. Flunarizine reduced head pain in postmenopausal women. However, the enhancement of both PRL and LH release indicates that this calcium antagonist might interfere with the dopaminergic tonus.

Topics: beta-Endorphin; Calcium Channel Blockers; Cinnarizine; Endorphins; Female; Flunarizine; Humans; Luteinizing Hormone; Menopause; Middle Aged; Migraine Disorders; Piperazines; Prolactin

Topics: Adult; Cinnarizine; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Random Allocation; Vasodilator Agents; Verapamil

The vestibular function was extensively investigated in 75 patients suffering from migraine. Pathological findings were present in 62 patients (82.6%). With the exception of position nystagmus, vestibular abnormalities were not related to migraine characteristics. Fifty-six patients were treated with flunarizine 10 mg daily for three months. A favourable effect on headache was obtained in 44 patients (78.5%). Flunarizine therapy influenced significantly gaze nystagmus and position nystagmus. The latter tended to be related to anti-migraine efficacy. Other electronystagmographic parameters were not substantially influenced. The authors assume that the vestibular abnormalities in migraine are side phenomena, the clinical relevance of which, at least during the headache-free phase, is not yet well understood.

Topics: Adolescent; Adult; Aged; Calcium Channel Blockers; Child; Cinnarizine; Electronystagmography; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Vestibular Function Tests; Vestibule, Labyrinth

Two new hypotheses suggest that the key pathology in migraine has a neuronal origin. A pivotal role is assigned to brain hypoxia (1) and spreading depression (SD) (neuronal depolarization spreading gradually over the cortex) (2). Flunarizine has been tested both against brain hypoxia and SD. Its potent antihypoxic properties in animal models led to its use as a prophylactic drug in migraine therapy. Earlier experiments suggested that flunarizine shortened recovery after neuronal depolarization. Recent experiments suggest that flunarizine may enhance the threshold for the elicitation of SD. Finally, it is often unclear whether the effects observed with flunarizine are due to a vascular or a direct neuronal effect. Therefore, a study was made to show whether flunarizine affected hypoxia-induced alterations in synaptic function in slices of hippocampus held in vitro. At physiological drug concentrations in brain, flunarizine improved post-hypoxic recovery of synaptic function. A direct neuronal protective effect was thus demonstrated.

Topics: Animals; Calcium Channel Blockers; Cells, Cultured; Cinnarizine; Cortical Spreading Depression; Disease Models, Animal; Flunarizine; Guinea Pigs; Hypoxia, Brain; Migraine Disorders; Neurons; Piperazines; Rats; Vasodilator Agents

Changes in erythrocyte deformability (ED) parameters have been investigated in 36 patients suffering from different forms of headache (classic and common migraine; migraine with interval headache; chronic tension headache) and treated with flunarizine (10 mg/day at bedtime). Patients were carefully selected in order to avoid any possible interference with the parameters under study, and smoke and drug use in particular (symptomatics included) were considered as criteria for exclusion from the trial. Controls of ED parameters were planned before treatment and after 20 and 35 days. Baseline ED alterations were present only among patients with chronic tension headache, but flunarizine treatment was able to positively modify ED parameters in these patients, as well as in migraine cases that showed normal baseline ED values. No correlation was found between patients' characteristics and baseline ED values, nor between ED changes under treatment and therapeutic effects of flunarizine.

Topics: Adult; Calcium Channel Blockers; Cinnarizine; Erythrocyte Deformability; Female; Flunarizine; Headache; Humans; Male; Middle Aged; Migraine Disorders; Piperazines

Fifty migraine patients were tested prior to and after a three-month period of flunarizine treatment (10 mg per day) by means of a new computerized telethermography apparatus. At completion of therapy a new computerized telethermography was carried out. The telethermographic data obtained showed an improvement in 70% of the cases; for the other patients telethermographic relevant modifications were not singled out.

Topics: Adult; Aged; Calcium Channel Blockers; Cinnarizine; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Ophthalmic Artery; Piperazines; Temperature; Thermography

BAEPs have been studied in a group of 20 migraine subjects before and after chronic flunarizine treatment. No statistically significant modifications of neurophysiological parameters have been observed. We confirm flunarizine effectiveness in migraine treatment.

Topics: Adult; Brain Stem; Calcium Channel Blockers; Cinnarizine; Evoked Potentials, Auditory; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Piperazines

In migraine patients the effect of calcium antagonists (flunarizine, verapamil and nifedipine) on both venous and pupillary neuromuscular functions, as well as on blood pressure have been evaluated. A single oral dose of flunarizine (10 mg) and verapamil infusion (50 micrograms/ml/min) increased venous compliance. Verapamil also counteracted dose-dependent dopamine induced venoconstriction. Nifedipine (10 mg orally) reduced mean arterial pressure in upright position in migraineurs but not in controls. In addition, chronic treatment with flunarizine (10 mg for 2 weeks) induced a transient miotic effect and a reduction of tyramine induced mydriasis. These findings demonstrated that calcium antagonists affect vascular and extravascular structures. It is postulated that, in migraine, calcium entry blockers may prevent exaggerated responses to catecholaminergic stimulation.

Topics: Blood Pressure; Calcium Channel Blockers; Cinnarizine; Flunarizine; Humans; Migraine Disorders; Nifedipine; Pupil; Vasoconstriction; Verapamil

The effect of 30-days of flunarizine (5 mg/day) therapy on pituitary, B-pancreatic, gonadic and adrenal function was studied in five adolescents with common migraine. Baseline concentration of growth hormone was significantly reduced after flunarizine therapy. The response of prolactin to thyrotrophin-releasing hormone was significantly increased after flunarizine therapy. The percentages of HbA1 and HbA1c were significantly higher after flunarizine therapy. The drug had no apparent effect on gonadic and adrenal function. Further studies are needed to confirm the effect of flunarizine on the hypothalamus-pituitary axis and glucose tolerance.

Topics: Adolescent; Adrenal Cortex Hormones; Calcium Channel Blockers; Child; Cinnarizine; Female; Flunarizine; Glycated Hemoglobin; Gonadal Steroid Hormones; Humans; Male; Migraine Disorders; Piperazines; Pituitary Hormones

Fifty-two patients, most of whom had had daily headaches for years, were examined and treated. Among them there were 40 who originally had migraine, the others had vasomotor or post-contusional headaches. Average duration of the migraine was 21 years, of chronic headache 7.6 years. All patients had been taking analgesics of a mixed type regularly and for a long time, on average 35.6 tablets or suppositories weekly. All patients had taken more than three different drugs. After an observation period of 3-6 months for grading the headaches and registering the amount of drug intake, all patients were admitted to hospital when all analgesics were at once discontinued. Changing degrees of withdrawal symptoms were the rule: increased headaches, nausea, vomiting, tachycardia, sweating, sleep disorders, and in some also hallucinations and cerebral episodes. At the end of the hospital stay chronic headache had completely disappeared or markedly improved in 77% of patients. Even after an average of 16 months of subsequent observation, chronic headache continued to be significantly improved in 70% of patients. There was a significant reduction in frequency and intensity of attacks in the patients with originally typical migraine. Regular intake of analgesics of the mixed type induces chronic headaches. These are most commonly caused by ergotamine tartrate and aminophenol derivatives, while psychological and physical dependence on anti-migraine drugs is initiated and maintained by additional barbiturates, caffeine and codeine.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Analgesics; Chronic Disease; Cinnarizine; Female; Flunarizine; Headache; Humans; Male; Middle Aged; Migraine Disorders; Pizotyline; Substance Withdrawal Syndrome

The effects of flunarizine in migraine headache were investigated in 40 patients treated with single 10 mg evening doses for 16 weeks. Standard criteria were adopted for patient admission and for the monitoring of clinical (headache index, consumption of analgesics, side-effects) and laboratory variables (platelet aggregation and red cells filterability). Significant positive effects were found in 31/40 cases irrespective of the clinical course of the disease (i.e., recurrent attacks or more or less chronic forms). Some baseline characteristics of the patients are discussed on the basis of the therapeutic response.

Topics: Adult; Analgesics; Asthenia; Cinnarizine; Erythrocyte Deformability; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Piperazines; Platelet Aggregation; Time Factors; Wakefulness

Topics: Adult; Calcium Channel Blockers; Cinnarizine; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Piperazines; Pizotyline; Thiophenes

Topics: Adult; Calcium Channel Blockers; Cinnarizine; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Piperazines

Topics: Calcium Channel Blockers; Cinnarizine; Flunarizine; Humans; Migraine Disorders; Piperazines

A REG study of 90 patients with migraine headaches demonstrated that a significant role in their genesis is played by regional hypertonia of cerebral vessels and phenomena of cerebral angiodystonia with a tendency towards spastic reactions rather than hypotonic. The use of stugeron for preventive treatment of migrain cephalgia was effective in 85 of the 100 treated patients and especially in those cases where there was an increased tone of the cerebral vessels according to the REG data. The most constant changes demonstrated by the REG were normalization of the vascular tone, more expressed in initial hypertone and to a less extent its influence on the cerebral blood flux (more frequently towards its increase and a decrease of hemispheric asymmetry). The authors consider it expedient to use REG methods when prescribing stugeron.

Topics: Adult; Cerebrovascular Circulation; Cinnarizine; Female; Humans; Male; Middle Aged; Migraine Disorders; Parasympatholytics; Piperazines; Plethysmography, Impedance

This work is an attempt to find an answer to the question: once arrived at the diagnostic identification of a certain type of idiopathic headache, which treatment should be followed? On the basis of recent researches and experience acquired during ten years' activity of our Headache Unit, a diagnostic identification can be made for migraine (in all its types and evolution stages), cluster headache, tension headache and pure psycogenic headache. Among the most widely used drugs, positive pharmacological results were obtained with: cyproheptadine, pizotifen, cinnarizine, lysergic acid derivatives, histamine, reserpine, clonidine and a barbituric acid derivative. The therapeutic cycles were standardized, for each drug, in the way of administration, dosage and total duration of the treatment. A comparison between the data obtained and the pre-therapeutic situation was made. When repeated, the most efficacious therapeutic cycle was evaluated. According to Pearson's dispersion index, each group of patients improved respresents 16.68% of the expected total results (frequency of attacks reduced to 50%, 25% and 0%): for cyproheptadine, pizotifen, methysergide, histamine, clonidine and allil-propyl-malonylurea, the "p" is less than 0.001; for cinnarizine, less than 0.02. This "a posteriori" analysis does not take into account the placebo control, the "anticipation effect", and the "carry over effect". It cannot therefore be a comparison of efficacy among the various drugs. An evaluation based on "among patients" and "inside patient" method by means of the cross over system, can instead give some useful suggestion about which treatment is to be recommended to patients suffering from recurrent headaches. With regard to migraine sufferers: cinnarizine, cyproheptadine, clonidine, histamine, pizotifen und reserpine. For cluster headaches: cinnarizine, cyproheptadine, clonidine, histamine and reserpine. For tension headaches: cyproheptadine. For pure psychogenic headache: allyl-propyl-malonylurea. For migraine attacks or parossystic crises in the course of ondulating or continuous headaches, positive therapeutic results, statistically significant, were obtained with an association of indomethacin, caffeine and prochlorperazine.

Topics: Cinnarizine; Clonidine; Cyproheptadine; Headache; Histamine; Humans; Methysergide; Migraine Disorders; Monoamine Oxidase Inhibitors; Peptides; Pizotyline; Reserpine; Urea; Vascular Headaches

Complicated migraine is regarded as a cerebrovascular syndrome of functional character. In the case of a young man with cervical migraine associated with paroxysmal neurological disorders and persisting EEG abnormalities, stellate ganglion blocks were performed under EEG control. A transient amelioration of the pathological EEG pattern was observed after each stellate ganglion block and after several treatments the EEG was normal and the migraine attacks disappeared. The pathophysiology of the effect of stellate ganglion block on cerebral blood flow is discussed.

Topics: Adult; Autonomic Nerve Block; Cinnarizine; Craniocerebral Trauma; Dihydroergotamine; Electroencephalography; Humans; Male; Migraine Disorders; Procaine; Pyrithioxin; Stellate Ganglion