flunarizine and Cerebrovascular-Disorders

Topics: Animals; Brain Ischemia; Calcium Channel Blockers; Calcium Channels; Cerebrovascular Disorders; Dihydropyridines; Flunarizine; Humans; Neuroprotective Agents; Verapamil

Medical treatment in acute stroke is probably more successful when started rapidly after the onset of symptoms. Therefore a drug is necessary which can be applied by the first physician prior to the diagnosis ischaemic versus haemorrhagic stroke by means of imaging methods. In animal models of ischaemic cerebral damage, a cerebroprotective effect of some calcium antagonists could be demonstrated, among them flunarizine and nimodipine. Flunarizine is effective also in experimental cerebral haemorrhage. The results of the first clinical trials with calcium antagonists are encouraging but inconclusive up to now. In view of the limited possibilities of treatment after a stroke, prevention is stressed.

Topics: Animals; Calcium; Calcium Channel Blockers; Cerebrovascular Disorders; Flunarizine; Nimodipine

Topics: Animals; Cerebrovascular Disorders; Cinnarizine; Dogs; Erythrocytes; Female; Flunarizine; Humans; Kinetics; Piperazines; Pregnancy; Rabbits; Tissue Distribution; Vasodilator Agents

Experience with flunarizine, a selective calcium-entry blocker, in the treatment of dizziness is reviewed. Clinical efficacy was predicted in pharmacological studies both in rabbits and humans: torsion swing or caloric induced nystagmus were significantly suppressed by flunarizine. Open therapeutic findings, using clinical and electronystagmographic or audiographic assessments as well, showed that flunarizine is of benefit to patients with vertigo of labyrinthine as well as of cerebrovascular origin. These results were confirmed in double-blind controlled trials. Flunarizine, either started with a loading dose gradually decreased thereafter, or given at a fixed 10 mg. dose schedule was proven to produce rapid improvement of dizziness and unsteadiness and to be tolerated very well.

Topics: Animals; Calcium Channel Blockers; Cerebrovascular Disorders; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Flunarizine; Humans; Labyrinth Diseases; Piperazines; Rabbits; Vertebrobasilar Insufficiency; Vertigo

Twenty-six patients with acute supratentorial brain infarction were randomly allocated to double-blind intravenous treatment with the calcium entry blocker flunarizine (12 patients) or placebo (14 patients) within 24 h. CT scan excluded other significant pathology. Impaired consciousness and gaze deviation were more common in the placebo group. Three patients in the treated group (25%) were either dead or severely disabled after 6 months, whereas this occurred in 8 of the 14 (57%) control patients, a difference of 32%. This difference is not statistically significant and there is an uneven distribution of important prognostic variables, however, the confidence limits of the difference (-4% and +68%) suggest that there may be a clinically important effect.

Topics: Aged; Aged, 80 and over; Calcium Channel Blockers; Cerebrovascular Disorders; Double-Blind Method; Female; Flunarizine; Humans; Ischemic Attack, Transient; Male; Middle Aged

Chronic cerebrovascular disorders (CCVD), as defined by the 1980 Ad Hoc Committee in Paris, constitute both clinically and pathogenetically an extremely complex entity, characterized by a protean symptom pattern. The effects of a daily dose of 10 mg flunarizine orally on CCVD have been evaluated with a neuropsychological methodology during a three-month treatment period in a randomized double-blind study compared with a placebo. The results confirmed the effectiveness of the drug in the improvement of neurological, amnesic, attentive and behavioural symptoms, without evident side-effects even after a long-term treatment.

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

A double-blind, double-dummy clinical trial was conducted in which the efficacy of cyclandelate 1600 mg daily was compared with that of flunarizine 10mg daily in 40 patients (25 men and 15 women) with dementia of cerebrovascular origin. Parameters were assessed before treatment, and after 45 and 90 days of therapy. At 90 days, significant improvements were observed in patients given cyclandelate in measurements of P100 latency in the left eye, neurological impairment, dementia scores, ischaemia scores, Gottfries mental deterioration scale, Hamilton depression scores, short term visual memory, long term memory, Bender-Gestalt test and Koh's blocks test. In flunarizine recipients, improvements were observed in neurological impairment, ischaemia scores, Gottfries scale and Hamilton depression scores. Patients treated with cyclandelate showed significantly greater ameliorations in symptoms as assessed by the ischaemia scale, evoked visual potential, visual memory and Koh's block test compared with those given flunarizine. However, in none of the parameters was flunarizine superior to cyclandelate.

Topics: Aged; Cerebrovascular Disorders; Clinical Trials as Topic; Cyclandelate; Dementia; Double-Blind Method; Electroencephalography; Evoked Potentials, Auditory; Female; Flunarizine; Humans; Male; Mandelic Acids; Memory; Middle Aged; Psychiatric Status Rating Scales; Random Allocation

In a clinically controlled double-blind study the effect of flunarizine (Sibelium) was compared with that of placebo in patients with involutional depression (WHO's International Classification of Diseases (ICD No. 296.0) and with cerebral circulatory disturbances (ICD No. 293.1). Effectiveness was objectified with the aid of the Clinical Global Impression test (CGI), the Hamilton Depression Scale (HAMD), the Nurses' Observation Scale for Inpatient Evaluation (NOSIE), and the "wellbeing tests" Bf-S and Bf-S'. Duration of treatment was 6 weeks. 32 patients were available for the final evaluation. In a combination of the good to excellent results considered as effective and the moderate to unsatisfactory results considered as ineffective the 82% rate of improvement in favour of the cerebral Ca2+ antagonist flunarizine was significantly superior to the 26% reached in the placebo group. The correlation with the psychopathometric tests has been proved. The medication was shown to be well tolerated. Side-effects did not appear. The mechanisms of action of the cerebral Ca2+ antagonist are discussed.

Topics: Adult; Aged; Cerebrovascular Disorders; Cinnarizine; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Random Allocation

Topics: Aged; Cerebrovascular Disorders; Chronic Disease; Cinnarizine; Clinical Trials as Topic; Drug Tolerance; Female; Flunarizine; Humans; Male; Middle Aged; Piperazines; Placebos

Experience with flunarizine, a selective calcium-entry blocker, in the treatment of dizziness is reviewed. Clinical efficacy was predicted in pharmacological studies both in rabbits and humans: torsion swing or caloric induced nystagmus were significantly suppressed by flunarizine. Open therapeutic findings, using clinical and electronystagmographic or audiographic assessments as well, showed that flunarizine is of benefit to patients with vertigo of labyrinthine as well as of cerebrovascular origin. These results were confirmed in double-blind controlled trials. Flunarizine, either started with a loading dose gradually decreased thereafter, or given at a fixed 10 mg. dose schedule was proven to produce rapid improvement of dizziness and unsteadiness and to be tolerated very well.

Topics: Animals; Calcium Channel Blockers; Cerebrovascular Disorders; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Flunarizine; Humans; Labyrinth Diseases; Piperazines; Rabbits; Vertebrobasilar Insufficiency; Vertigo

The hemorheological effect of KB-2796, 1-[bis(4-fluorophenyl)methyl]-4-(2,3,4,-trimethoxybenzyl)piperazine dihydrochloride, was studied in guinea pigs and rabbits in comparison with those of flunarizine (FNZ) and pentoxifylline (PXF). KB-2796 and FNZ at 10-100 microM dose-dependently prevented crenation of rabbit erythrocytes induced by the Ca2+ ionophore A23187. After incubation of guinea pig whole blood at 37 degrees C, blood micropore-filterability decreased and blood viscosity increased with the progress of erythrocyte crenation. After a 4-hr incubation, KB-2796 inhibited erythrocyte crenation and decreased blood filterability at a concentration of 30 microM, and it increased blood viscosity at 10 microM. Treatment with FNZ (30 microM) and PXF (100 microM) also inhibited erythrocyte crenation and decreased blood filterability. Intravenous administration of KB-2796 at 3 mg/kg significantly inhibited the decrease of blood micropore-filterability after occlusion of the bilateral carotid arteries in rabbits. Although FNZ (3 mg/kg, i.v.) had no effect, PXF (3 mg/kg, i.v.) produced significant inhibition. These results suggest that KB-2796 prevents increase of blood viscosity and decrease of blood filterability by inhibiting the crenation of erythrocytes and suggest that this effect may be useful for the improvement of hemorheology in ischemic disease.

Topics: Animals; Blood Viscosity; Calcium Channel Blockers; Cerebrovascular Disorders; Erythrocyte Deformability; Flunarizine; Guinea Pigs; In Vitro Techniques; Male; Micropore Filters; Pentoxifylline; Piperazines; Rabbits

A series of 11-[4-(cinnamyl)-1-piperazinyl]-6,11-dihydrodibenz[b,e] oxepins and related compounds were synthesized and evaluated for their protective activities against complete ischemia, normobaric hypoxia, lipidperoxidation and convulsion. Structure-activity relationship studies of this series led to the finding of (E)-1-(3-fluoro-6,11-dihydrodibenz[b,e]oxepin-11-yl)-4-(3- phenyl-2-propenyl)piperazine dimaleate (50), AJ-3941 with the most appropriate property for combined pharmacological activities. Compound 50 also shows an inhibitory effect against cerebral edema as well when orally given to rats.

Topics: Animals; Benzothiepins; Benzoxepins; Brain Edema; Brain Ischemia; Cerebrovascular Disorders; Flunarizine; Hypoxia, Brain; Mice; Piperazines; Rats; Structure-Activity Relationship

The effect of the calcium entry blockers flunarizine and nimodipine on isolated human cerebral and temporal arteries has been studied. Flunarizine induced only weak relaxation of precontracted temporal arteries in contrast to the response seen in cerebral arteries. Nimodipine invariably induced strong relaxation of both types of vessel. The effect of the calcium entry blockers on potassium (K+)-, noradrenaline (NA)- and 5-hydroxytryptamine (5-HT)-induced contraction was also examined. In general, the K(+)-induced contraction was inhibited by both calcium entry blockers, nimodipine being more potent than flunarizine, the cerebral artery being more sensitive. The response to K+ consisted of two phases; the second, slowly developing phase of contraction was more sensitive to either blocker than the initial, fast phase of contraction. Flunarizine was significantly more potent in inhibiting NA-induced contraction of the human cerebral than of the temporal artery, and there was no difference in its action on 5-HT-induced contraction of either artery. The same pattern was found for nimodipine, which was more potent in every aspect. Both calcium entry blockers induced a parallel shift in calcium-induced contraction studied by application of calcium to vessels preincubated in calcium free medium. Flunarizine was more potent on cerebral than on temporal arteries and there was no difference between the two vessels in this action of nimodipine. However, the latter was more potent than flunarizine in preventing calcium-induced contraction. The clinical implications of the two agents are discussed in relation to cerebrovascular disorders.

Topics: Calcium; Cerebral Arteries; Cerebrovascular Disorders; Flunarizine; Humans; Migraine Disorders; Nimodipine; Norepinephrine; Potassium; Serotonin; Temporal Arteries; Vasoconstriction

Topics: Calcium Channel Blockers; Cerebral Infarction; Cerebrovascular Disorders; Epilepsy; Flunarizine; Humans; Intracranial Arteriosclerosis; Migraine Disorders; Nimodipine

Baroreflex sensitivity assessed by phenylephrine-induced reflex bradycardia was markedly decreased by 5- an 10-min global cerebral ischemia in anesthetized dogs. Flunarizine, 0.1 and 1 mg/kg i.v., administered 5 min prior to 5-min ischemia, completely inhibited the decrease in baroreflex sensitivity while such a protective effect of the latter dose was incomplete against 10-min ischemia. In contrast, papaverine, 0.5 mg/kg per min i.v., infused for 5 min prior to 5-min ischemia, failed to protect the decrease in baroreflex sensitivity. Flunarizine may possess a certain direct cerebroprotective effect in addition to its cerebrocirculatory effect.

Topics: Animals; Blood Pressure; Cerebrovascular Disorders; Dogs; Dose-Response Relationship, Drug; Female; Flunarizine; Heart Rate; Ischemic Attack, Transient; Male; Papaverine; Pressoreceptors; Reflex

Thromboembolic brain ischemia was produced in dogs using an autologous blood clot model. The effect of postembolic treatment with flunarizine and streptokinase on hemispheric cerebral metabolic rate for oxygen (CMRO2), oxygen extraction ratio (OER), and cerebral blood flow (CBF) was studied by positron emission tomography (oxygen-15 technique) 24 hours after the insult. We studied five groups of experimental dogs and compared them with a control group of nonembolized dogs. Group I received no treatment, Group II was treated locally with 500,000 IU streptokinase starting 30 minutes after the insult, Group III received streptokinase locally 30 minutes after the insult and 0.1 mg/kg i.v. flunarizine immediately after the insult and 2 hours later, Group IV received flunarizine as Group III, and Group V was orally pretreated with 0.5 mg/kg/day flunarizine during 2 weeks preceding embolization. Compared with the contralateral hemisphere, in the embolized hemisphere a significant reduction of CMRO2 (-25% to -40%) and CBF in normocapnia (-35%) and hypercapnia (-50%) was observed in Groups I, II, and V. In Groups III and IV, CMRO2, OER, and CBF of the embolized hemisphere were within the normal range during normocapnia and hypercapnia; the extent of the ischemic lesions was markedly less than in the other groups of experimental dogs. We conclude that flunarizine treatment after experimental thromboembolic stroke had a favorable influence on brain tissue. Chronic preventive flunarizine treatment failed to have a beneficial effect.

Topics: Animals; Brain; Calcium Channel Blockers; Cerebrovascular Circulation; Cerebrovascular Disorders; Dogs; Female; Flunarizine; Intracranial Embolism and Thrombosis; Male; Oxygen Consumption; Streptokinase

Topics: Adolescent; Cerebrovascular Disorders; Chromatography, Gas; Epilepsy; Female; Flunarizine; Half-Life; Humans; Indicators and Reagents

Topics: Adult; Aged; Aged, 80 and over; Basal Ganglia Diseases; Cerebrovascular Disorders; Cinnarizine; Female; Flunarizine; Humans; Male; Middle Aged; Placebos

Acute ischemia of the brain induces a cascade of biochemical and physiological events. The final consequences depend on the fact whether ischemia is of transient or permanent, total or partial nature. Alteration of extracellular potassium concentration, intracellular calcium and potassium concentration, development of cytotoxic and vasogenic edema, postischemic hyperfusion and no-reflow phenomenon are important factors which decide about the final fate of functional capacity. CO2 reactivity, autoregulation and hemorheology must be considered when therapeutic approaches are used to influence basic flow during ischemic condition. At present there exists no therapy which has been fully accepted and is able to guarantee benefit to the hypoperfused tissue. Since the calcium metabolism is altered by ischemic processes, substances which act on this metabolism might be of value in the treatment of ischemia and its consequences. However, their beneficial effect on cerebral infarction has not been proven yet. In subarachnoid hemorrhage and migraine calcium antagonists are used to prevent and treat ischemia. In epilepsia calcium overload blockers have been tried by one group with promising results.

Topics: Acute Disease; Brain Edema; Brain Ischemia; Calcium Channel Blockers; Cerebrovascular Disorders; Epilepsy; Flunarizine; Humans; Migraine Disorders; Rheology; Subarachnoid Hemorrhage

Retinal fluorangiographic techniques can be employed in the study of cerebrovascular disorders in relation to the embryological, anatomic and functional affinities between the cerebral and retinal circulation. The techniques currently used have been improved by means of the computer analysis of the photographic image, thus allowing qualitative evaluations of the vascular dynamics and quantitative evaluations referred to remarkable variations. These improved techniques can be summed up as follows: equidensitometry with arbitrary colors, computerized fluorangiography for the evaluation of the vascular caliber, computer analysis of mean transit time (m.t.t.). A new type of qualitative evaluation not considering the fluorangiographic image has recently been introduced: the fluorophotometric analysis.

Topics: Adult; Aged; Capillary Permeability; Cerebrovascular Circulation; Cerebrovascular Disorders; Cinnarizine; Computers; Female; Flunarizine; Fluorescein Angiography; Humans; Male; Middle Aged; Radiography; Retinal Vessels; Vasodilator Agents

Topics: Aged; Brain Ischemia; Cerebrovascular Disorders; Cinnarizine; Female; Flunarizine; Humans; Male; Piperazines; Vasodilator Agents

Topics: Adult; Aged; Arterial Occlusive Diseases; Cerebrovascular Disorders; Cinnarizine; Female; Flunarizine; Humans; Male; Middle Aged; Piperazines; Raynaud Disease; Vasodilator Agents