cinnarizine and Cerebrovascular-Disorders

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

While their importance in the market-place is steadily increasing in developed (mainly continental Europe) and even in developing countries, compounds included in the broad category of 'cerebroactive' drugs hardly rate a mention in reference pharmacology and therapeutics textbooks. It is an undeniable fact, however, that the principal users or targets of this drug class, mainly elderly people, represent an increasingly worrying problem, with their often puzzling cohort of ill-definable and even less predictable neurological and mental symptoms. The combination of the above factors cannot but produce a rather confused situation, in which the pressure to treat and the adherence to scientifically rigorous assessment are likely to prevail alternately, on a purely casual basis. This review aims to provide sound methodological guidelines for assessment of 'cerebroactive' drugs in a not always easily accessible literature. It covers firstly the general problems of stroke, dementia and 'common symptoms' of the elderly, and then looks in detail at those compounds which have to date attracted most attention (ergot derivatives, cinnarizine, flunarizine, vincamine, eburnamonine, naftidrofuryl, oxpentifylline, piracetam and citicoline), as well as those which are currently considered investigational (choline and lecithin). The pharmacology and available clinical studies of each drug are examined. No therapeutic indication can be derived from the available evidence, as the few positive results do not go beyond random improvement of symptoms. More fundamentally, the lines of research which need to be pursued most intensively relate to better preliminary definition of diagnostic and prognostic criteria and, with the establishment of adequate testing tools for the assessment of behaviour and neuropsychological performance, those basal conditions which are modified 'naturally' or by drugs.

Topics: Adult; Aged; Cerebrovascular Disorders; Cinnarizine; Clinical Trials as Topic; Cytidine Diphosphate Choline; Dementia; Dihydroergotoxine; Humans; Middle Aged; Nafronyl; Pentoxifylline; Piracetam; Vasodilator Agents; Vincamine

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

Topics: Aged; Animals; Betahistine; Cerebrovascular Circulation; Cerebrovascular Disorders; Cinnarizine; Clinical Trials as Topic; Dementia; Dihydroergotoxine; Humans; Isoxsuprine; Nicotinic Acids; Nylidrin; Rats; Receptors, Adrenergic; Receptors, Histamine; Vasodilator Agents; Vincamine

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

While their importance in the market-place is steadily increasing in developed (mainly continental Europe) and even in developing countries, compounds included in the broad category of 'cerebroactive' drugs hardly rate a mention in reference pharmacology and therapeutics textbooks. It is an undeniable fact, however, that the principal users or targets of this drug class, mainly elderly people, represent an increasingly worrying problem, with their often puzzling cohort of ill-definable and even less predictable neurological and mental symptoms. The combination of the above factors cannot but produce a rather confused situation, in which the pressure to treat and the adherence to scientifically rigorous assessment are likely to prevail alternately, on a purely casual basis. This review aims to provide sound methodological guidelines for assessment of 'cerebroactive' drugs in a not always easily accessible literature. It covers firstly the general problems of stroke, dementia and 'common symptoms' of the elderly, and then looks in detail at those compounds which have to date attracted most attention (ergot derivatives, cinnarizine, flunarizine, vincamine, eburnamonine, naftidrofuryl, oxpentifylline, piracetam and citicoline), as well as those which are currently considered investigational (choline and lecithin). The pharmacology and available clinical studies of each drug are examined. No therapeutic indication can be derived from the available evidence, as the few positive results do not go beyond random improvement of symptoms. More fundamentally, the lines of research which need to be pursued most intensively relate to better preliminary definition of diagnostic and prognostic criteria and, with the establishment of adequate testing tools for the assessment of behaviour and neuropsychological performance, those basal conditions which are modified 'naturally' or by drugs.

Topics: Adult; Aged; Cerebrovascular Disorders; Cinnarizine; Clinical Trials as Topic; Cytidine Diphosphate Choline; Dementia; Dihydroergotoxine; Humans; Middle Aged; Nafronyl; Pentoxifylline; Piracetam; Vasodilator Agents; Vincamine

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

Topics: Bencyclane; Cerebrovascular Disorders; Cinnarizine; Double-Blind Method; Humans; Nicergoline; Pyrrolidines; Vasodilator Agents

Topics: Aged; Animals; Betahistine; Cerebrovascular Circulation; Cerebrovascular Disorders; Cinnarizine; Clinical Trials as Topic; Dementia; Dihydroergotoxine; Humans; Isoxsuprine; Nicotinic Acids; Nylidrin; Rats; Receptors, Adrenergic; Receptors, Histamine; Vasodilator Agents; Vincamine

In this paper a comparison was established from the clinical, neurological, psychological, and laboratory viewpoints, between the effects on the cental nervous system of a vasodilating medication, cinnarizine, currently accepted as effective, and buflomedil, a medicine recently introduced, which has shown good promise in the treatment of peripheral vascular diseases. During a 180-day period, 37 patients suffering from vascular cerebral insufficiency, aged between 43 and 86 years, were treated. The patients were randomized into two groups, each group receiving one of the treatments in a double-blind study. All patients were periodically administered clinical and neurological tests, and the Benton Test for visuo retention through which the intellectual level, recent memory, and visuo-motor coordination were examined. In addition, the patients were given a series of laboratory toxicity tests to ascertain the safety of the treatment. On completion of the study all data submitted to a statistical analysis. After studying the results, the authors reached the conclusion that both treatments were beneficial; when corresponding doses were used, buflomedil showed better results by improving the reasoning and the remote memory, and in the Benton test, better results in improving visuo-motor coordination were demonstrated by statistical analysis. Laboratory tests did not reveal any changes except in the serum cholesterol level, which decreased significantly in those patients who took buflomedil.

Topics: Aged; Blood Pressure; Cerebrovascular Disorders; Cholesterol; Cinnarizine; Double-Blind Method; Female; Humans; Male; Neurologic Manifestations; Piperazines; Psychological Tests; Pyrrolidines; Sleep

Topics: Arteriosclerosis; Calcium; Cerebrovascular Disorders; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Humans; Intermittent Claudication; Leg Ulcer; Paresthesia; Piperazines; Vascular Diseases; Vasodilator Agents; Venous Insufficiency

Plasma levels were measured at different times during long-term flunarizine treatment (duration 1--45 months, median: 6 months) of 50 patients with intermittent claudication. The dose was gradually reduced, within one month, from an initial dose of 30 mg daily to a maintenance dose of 10 mg daily. Plasma levels, measured by HPLC-method, showed considerable individual differences, ranging between less than 0.02 microgram/ml and 0.25 microgram/ml. Levels between 0.05 and 0.1 microgram/ml were found in 46% of the patients. Individual measurements clearly showed dose-related plasma-levels. There were no signs of accumulation. Side-effects were related to the dose rather than to the levels. There was no correlation between clinical improvement and plasma levels. An extensive first-pass metabolism in the liver is suggested as a possible explanation for the varying inter-individual plasma levels.

Topics: Adult; Aged; Cerebrovascular Disorders; Cinnarizine; Clinical Trials as Topic; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Piperazines; Time Factors

The results of a double blind trial in a total of 54 outpatients with cerebrovascular insufficiency are reported. With reference to objective test criteria (flicker frequency analysis and reaction test) and the change in the existing symptoms of this clinical picture the behavior of a new preparation, Cetal retard, was compared with the well-known drug (cinnarizine) with regard to the therapeutic efficacy on these symptoms. Although a therapeutic success was demonstrable in both groups after 21 days, Cetal retard was found to be significantly better in a number of the criteria tested.

Topics: Aged; Attention; Cerebrovascular Disorders; Cinnarizine; Clinical Trials as Topic; Delayed-Action Preparations; Double-Blind Method; Female; Flicker Fusion; Headache; Humans; Male; Middle Aged; Piperazines; Reaction Time; Sleep Wake Disorders; Vertigo; Vinca Alkaloids

Topics: Aged; Brain; Cerebrovascular Disorders; Cinnarizine; Electroencephalography; Humans; Laser Therapy; Methods; Middle Aged; Plethysmography, Impedance; Vasodilator Agents; Vinca Alkaloids

A single-dose cinnarizine (25 and 75 mg) was compared to its course administration (75 and 225 mg/day) in 35 patients with circulatory encephalopathy. Upon a 3-fold increase in conventional doses, there appeared more profound clinical, vasomotor cerebral and functional cerebral effects as evidenced by EEG and neuropsychological tests.

Topics: Adult; Aged; Cerebrovascular Disorders; Cinnarizine; Dose-Response Relationship, Drug; Drug Evaluation; Electroencephalography; Female; Humans; Hypertension; Intracranial Arteriosclerosis; Male; Middle Aged; Neuropsychological Tests

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

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

Topics: Aminophylline; Anticoagulants; Antihypertensive Agents; Brain Edema; Cerebrovascular Disorders; Cinnarizine; Cyclandelate; Humans; Ischemic Attack, Transient; Nifedipine; Papaverine; Vincamine

Topics: Cerebrovascular Disorders; Cinnarizine; Delayed-Action Preparations; Double-Blind Method; Family Practice; Flicker Fusion; Humans; Reaction Time; Surveys and Questionnaires; Vinca Alkaloids; Vincamine

Topics: Aged; Cerebrovascular Disorders; Cinnarizine; Drug Evaluation; Female; Humans; Male; Middle Aged; Piperazines; Vinca Alkaloids

Topics: Blood Coagulation Disorders; Cerebrovascular Disorders; Cinnarizine; Drug Evaluation; Female; Humans; Male; Piperazines

Topics: Aged; Animals; Cerebellum; Cerebrovascular Disorders; Cinnarizine; Guinea Pigs; Humans; Muscle Contraction; Piperazines; Rabbits; Rats; Vestibule, Labyrinth

Topics: Aged; Cerebrovascular Circulation; Cerebrovascular Disorders; Cinnarizine; Drug Evaluation; Female; Humans; Hypersensitivity; Male; Middle Aged; Piperazines

Topics: Adult; Aged; Cerebrovascular Circulation; Cerebrovascular Disorders; Cinnarizine; Collateral Circulation; Female; Humans; Male; Middle Aged; Piperazines; Vasodilator Agents