flunarizine and Body-Weight

This study was designed to compare flunarizine, a cerebro-specific calcium channel antagonist, and propranolol in the prophylaxis of migraine with or without aura. Following a 1 month single-blind placebo baseline period, 94 patients were equitably randomised under double-blind conditions to take flunarizine 10 mg daily or propranolol 80 mg twice daily for 4 months. Both treatments led to a significant reduction in the frequency of migraines and use of rescue analgesics with a significantly greater decrease in number of attacks for flunarizine after 1 and 4 months. Neither treatment affected the severity nor duration of migraines. Overall, 67% of flunarizine patients and 51% of propranolol patients responded positively. Propranolol significantly reduced blood pressure and heart rate; flunarizine had no effect on cardiovascular function. Weight gain was noted with both treatments. Flunarizine is at least as effective as propranolol in the prophylactic treatment of migraine and may have a better safety profile.

Topics: Adolescent; Adult; Aged; Body Weight; Canada; Double-Blind Method; Female; Flunarizine; Hemodynamics; Humans; Male; Middle Aged; Migraine Disorders; Propranolol; Single-Blind Method

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

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

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

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

This study was aimed to evaluate the protective effect of flunarizine on cisplatin-induced acute renal failure. Administration of cisplatin (6 mg/kg, i.p. on day 6) significantly increased serum blood urea nitrogen and creatinine, urinary N-acetyl β-D-glucosaminidase, tissue thiobarbituric acid reactive substances and total calcium whereas, decreased body weight, fractional excretion of sodium, creatinine clearance tissue-reduced glutathione, mitochondrial cytochrome c oxidase, and ATP levels were observed in acute renal failure rats. Moreover, cisplatin produced histopathological changes in the renal tissue. Furthermore, flunarizine (100, 200, and 300 μM/kg, p.o., for six consecutive days) was administered to evaluate its therapeutic potential in acute renal failure, and the results were compared with cyclosporin A (50 μM/kg, p.o., for six consecutive days) as a reference drug. Flunarizine resulted in the attenuation of cisplatin-induced renal dysfunction, oxidative stress marker, mitochondrial damage, and histopathological changes in rats. Medium and higher doses of flunarizine produced significant renal protective effect which was comparable to cyclosporin A. The results of this study clearly revealed that flunarizine protected the kidney against the nephrotoxic effect of cisplatin via mitochondrial permeability transition pore inactivation potential.

Topics: Acetylglucosaminidase; Acute Kidney Injury; Adenosine Triphosphate; Animals; Blood Urea Nitrogen; Body Weight; Calcium; Cisplatin; Creatinine; Cyclosporine; Electron Transport Complex IV; Female; Flunarizine; Glutathione; Kidney; Mitochondria; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Rats; Rats, Sprague-Dawley; Sodium; Thiobarbituric Acid Reactive Substances

This study was aimed to evaluate the role of flunarizine on gentamicin (GEM) induced nephrotoxicity in rat. Administration of GEM (40 mg/kg, s.c. for 10 consecutive days) significantly increased blood urea nitrogen (BUN), N-acetyl β-d-glucosaminidase (NAG), thiobarbituric acid reactive substances (TBARS) and total calcium whereas, decreased body weight, fractional excretion of sodium (FrNa), creatinine clearance (CrCl), reduced glutathione (GSH), mitochondrial cytochrome c oxidase (Cyt-C oxidase) and ATP levels resulting in nephrotoxicity. Further, flunarizine (100, 200 and 300 µmol/kg, p.o.) was administered to evaluate its renoprotective effect against GEM induced nephrotoxicity and the results were compared with cylcosporin A (CsA, 50 µmol/kg, p.o.). Flunarizine resulted in the attenuation of renal dysfunction and oxidative marker changes in rats subjected to GEM induced nephrotoxicity in a dose dependent manner. Medium and higher doses of flunarizine produced significant renal protective effect which was comparable to cyclosporin A. The results of this study clearly revealed that flunarizine protected the kidney against the nephrotoxic effect of GEM via mitochondrial permeability transition pore (MPTP) inactivation potential.

Topics: Animals; Body Weight; Cyclosporine; Flunarizine; Gentamicins; Kidney Diseases; Male; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Rats; Rats, Sprague-Dawley

A localized atheromatous plaque was induced in rabbits after transmural electrical stimulation of the carotid and a cholesterol-rich diet (1.33% cholesterol) for 4 weeks. This model was used to investigate the antiatherogenicity of indapamide. The treatment given per os started 14 days before the stimulation period. Animals were divided into six groups: group 1 (control) received gelatin 2%, group 2 received hydrochlorothiazide at 20 mg/kg/day, group 3 was treated with flunarizine at 25 mg/kg/day, and groups 4, 5, and 6 received indapamide at 0.3, 1, and 3 mg/kg/day, respectively. During the experimental period, all rabbits showed similar weight gain, regardless of the treatment. Image analysis showed an antiatherogenic effect for indapamide (0.3 mg/kg/day) characterized by a reduction in the number of cell layers (NCL; 10.5 +/- 1.8 vs. 18.0 +/- 2.9; p < 0.05) and in the intima/media area ratio (I/M; 17.5 +/- 4.5 vs. 42.7 +/- 7.0%; p < 0.01). Indapamide appeared to be more active than the reference drug flunarizine (NCL = 14.2 +/- 2.5, N.S.; I/M = 24.5 +/- 4.3, p < 0.05). The maximum effect occurred at the lowest dose tested (0.3 mg/kg/day). The reason for the loss of antiatherogenic activity of indapamide at higher doses is discussed. Hydrochlorothiazide did not show any effect on the formation of the atheromatous plaque.

Topics: Animals; Arteriosclerosis; Basement Membrane; Body Weight; Carotid Arteries; Cell Division; Cholesterol, Dietary; Disease Models, Animal; Electric Stimulation; Flunarizine; Hydrochlorothiazide; Image Processing, Computer-Assisted; Indapamide; Male; Rabbits; Tunica Intima

The calcium antagonist flunarizine (FLN) was tested for its ability to prevent doxorubicin (DXR)-induced cardiotoxicity in the rat. A cumulative dose of 9.0 mg/kg of DXR was administered i.v. over a period of 1 week. FLN (10 mg/kg/day i.p., 6 days/week) was administered according to two different time schedules, covering respectively the first and last 4 weeks after the beginning of DXR treatment. The two schedules were adopted to assess whether early and/or delayed DXR-induced cardiotoxic effects were affected by FLN. The development of cardiac toxicity was monitored by ECG recordings. The animals were sacrificed 8 weeks after the beginning of DXR treatment. The contractile performance of isolated atria and the morphological pattern of left ventricular fragments were subsequently evaluated. The early administration schedule of FLN was shown to be ineffective in preventing DXR-induced cardiotoxicity and in some cases was actually found to potentiate the effects of DXR. In contrast, the histological evaluation of ventricular preparations from rats treated with DXR and FLN according to the delayed time schedule showed a significant improvement with respect to hearts from animals treated with DXR alone. An inhibition of the delayed calcium overload occurring after DXR administration has been proposed as a possible mechanism for this protective action.

Topics: Animals; Body Weight; Calcium Channel Blockers; Doxorubicin; Drug Administration Schedule; Electrocardiography; Female; Flunarizine; Heart; In Vitro Techniques; Myocardial Contraction; Myocardium; Rats; Rats, Inbred Strains

Topics: Adolescent; Adult; Body Weight; Drug Administration Schedule; Female; Flunarizine; Headache; Humans; Male; Middle Aged; Migraine Disorders; Sex Factors

The effects of two calcium channel blockers (verapamil and flunarizine) were evaluated on the naloxone-precipitated syndrome in morphine-dependent rats. The withdrawal signs in saline-treated rats were mainly diarrhea, body weight loss, jumping and ptosis. On i.p. administration, verapamil and flunarizine prevented diarrhea and body weight loss but not jumping. Verapamil also reduced the incidence of ptosis at the highest dose tested (40 mg/kg). Administered i.c.v., 160 micrograms verapamil reduced the body weight loss and the number of jumps without modifying diarrhea or ptosis. The results show that calcium channel blockers inhibit morphine abstinence syndrome manifestations through both peripheral and central mechanisms.

Topics: Animals; Body Weight; Brain; Calcium Channel Blockers; Clonidine; Diarrhea; Flunarizine; Injections, Intraventricular; Male; Morphine Dependence; Naloxone; Rats; Substance Withdrawal Syndrome; Verapamil