flunarizine and Parkinson-Disease--Secondary

Secondary parkinsonism induced by exposure to dopamine (DA) receptor antagonists as first and second generation antipsychotics, DA storage depleters, calcium channel blockers, benzamides substituted and other classes of drugs is traditionally believed to be completely reversible in most of patients following withdrawal of the offending drug even though after a variable time delay. The lack of recovery or initial full recovery with subsequent development of progressive parkinsonism has been regarded to result from an underlying subclinical degenerative process like PD unmasked by the inducing drug. These well-recognized clinical outcomes of drug-induced parkinsonism (DIP) have disregarded the existence of another outcome, characterized by permanent non-progressive parkinsonism. This syndrome may fullfil the criteria of tardive parkinsonism, a controversial entity currently referred to as a persistent condition without indication of its long-term course and clinical features. On reviewing the published literature on DIP, we have identified two prospective long-term follow-up of elderly patients in which parkinsonism induced by the calcium channel antagonists cinnarizine and flunarizine became permanent and non-progressive following drug discontinuation in a non-negligible proportion of patients, consistent with the clinical concept of a true tardive syndrome, according to currently accepted criteria. The authors hypothesize that the development of tardive parkinsonism might be due to a neurotoxic effect of the pharmacodynamic proprieties of the calcium channel blockers and their metabolites, exerted on post-synaptic striatal neurons and/or a neurotoxic damage on presynaptic DA neurons in patients without an underlying subclinical degenerative parkinsonism, so accounting for the stable and non-progressive course over time.

Topics: Aged; Antipsychotic Agents; Calcium Channel Blockers; Cinnarizine; Dopamine Antagonists; Flunarizine; Humans; Parkinson Disease, Secondary; Parkinsonian Disorders; Prospective Studies; Syndrome

Aged people are frequently the victims of iatrogenic diseases, especially adverse effects of drugs since they are affected by many age-related diseases and are given many drugs. Geriatric medicine in Japan has a bitter history of having produced many victims by adverse effects of cerebral vasodilators and cerebral stimulants; they included parkinsonism and depression induced by flunarizine and cinnarizine, and Reye-like encephalopathy induced by calcium hopantenate. Parkinsonism induced by sulpiride, tiapride, metoclopramide or atypical anti-psychotics, dyskinesia induced by anti-parkinsonian drugs or anti-psychotics, and psychotic symptoms induced by anti-parkinsonian drugs, anti-cholinergic drugs, anti-depressants or histamine H2 antagonists are still very common. Wernicke encephalopathy caused by intravenous glucose infusion without thiamine, central pontine myelinolysis by too rapid correction of hyponatremia are important though infrequent. Iatrogenic Creutzfeldt-Jakob disease by dura grafts is a warning against the easy use of medical materials produced with human organs or blood. Iatrogenic diseases are preventable, and geriatricians have to pay attention to the information on adverse effects of drugs and medical materials and carefully observe the early signs of iatrogenic diseases.

Topics: Aged; Cinnarizine; Creutzfeldt-Jakob Syndrome; Flunarizine; Humans; Iatrogenic Disease; Medication Errors; Nervous System Diseases; Parkinson Disease, Secondary; Psychoses, Substance-Induced; Wernicke Encephalopathy

Drug-Induced Parkinsonism (DIP) represents the second leading cause of Parkinsonism (PK) in several countries. Flunarizine and cinnarizine are some of the most common drugs that cause DIP. This paper reviews the first description of Flunarizine and Cinnarizine-Induced Parkinsonism (FCIP), as well as the subsequent literature, emphasizing epidemiological, clinical and diagnostic aspects.. We reviewed the literature on the subject, with special emphasis on the first description and the later definition of the clinical syndrome that results from chronic use of flunarizine and cinnarizine.. In 1984, De Melo-Souza reported the first description of flunarizine-induced PK in five patients. Other reports followed on FCIP, emphasizing the clinical features, which are symmetrical parkinsonism, and depression, affecting mainly elderly women.. Eighteen years after the original description, FCIP is a recognized condition with specific clinical features, and is the second most common cause of parkinsonism in many countries.

Topics: Cinnarizine; Flunarizine; Humans; Parkinson Disease, Secondary

The authors report the case of a female patient with parkinsonism induced by flunarizine, and refer the tremor to be of parkinsonian and also of wilsonian type. Cure was observed within three months, after withdrawal of flunarizine, and the use of L-dopa and biperiden.

Topics: Biperiden; Female; Flunarizine; Humans; Levodopa; Middle Aged; Parkinson Disease, Secondary

Topics: Calcium Channel Blockers; Clinical Trials as Topic; Double-Blind Method; Flunarizine; Humans; Hypertension; Parkinson Disease, Secondary

Flunarizine (fz) causes side effects such as movement disorders (MDs). We investigated risk factors associated with fz-related MDs. Participants were recruited from the longitudinal health insurance databases and included patients who took fz for more than 1 month. Patients with one of the underlying diseases, or with concomitant drug use (antipsychotics, metoclopramide or reserpine), and those diagnosed with MDs before fz use were excluded. Fz-related MD was defined as a new diagnosis of parkinsonism or hyperkinetic syndrome including dyskinesia or secondary dystonia during fz use or within 3 months after drug discontinuation. After exposure, 288 individuals had fz-related MDs (parkinsonism, n = 240; hyperkinesia, n = 48). Risk factors associated with these disorders were higher-dose exposure (cumulative defined daily dose [cDDD] ≥87.75, odds ratio [OR]: 3.80; 95% CI: 2.61-5.52), older age (OR: 1.07; 95% CI: 1.06-1.09), history of essential tremor (OR: 6.39; 95% CI: 2.29-17.78) and cardiovascular disease (CVD) (OR: 1.47; 95% CI: 1.14-1.9). The optimal value of cDDD to predict MDs was 58.5 (sensitivity: 0.67, specificity: 0.60), indicating an overall exposure of 585 mg. Higher exposure dose and duration, older age, history of essential tremor, and CVD were associated with fz-associated MDs. Clinicians ought to watch for extrapyramidal side effects when prescribing fz.

Topics: Aged; Case-Control Studies; Databases, Factual; Female; Flunarizine; Humans; Hyperkinesis; Insurance, Health; Male; Middle Aged; Parkinson Disease, Secondary; Risk Factors

Single intrastriatal microinjections of 25, 50 and 100nmol/microl of flunarizine in normal rats produced a dose-dependent turning behavior toward the injected side when they were challenged with apomorphine (1mg/kg, s.c). This effect was seen at 1, 3 and 7 days following administration of the high dose of flunarizine, but had subsided by 24h after administration of the intermediate dose; the low dose was ineffective. However, intrastriatal injection of the high dose of flunarizine resulted in a local lesion and thereafter this dose was not used. A similar dose-response relationship was determined for nifedipine, an L-type calcium channel antagonist. Injection of this antagonist did not result in apomorphine-elicited rotational behavior, reflecting its lack of antidopaminergic action. Intrastriatal injections of haloperidol (5microg/microl), an antagonist of dopamine D(2) receptors, or the sodium channel blocker lidocaine (40microg/microl), were given in order to compare their effects to those observed with flunarizine. Intracerebral injection of haloperidol produced ipsilateral turning in response to systemic administration of apomorphine given 60min after. The same response was obtained with the injection of apomorphine 10min after the injection of intracerebral lidocaine. This effect was no longer apparent 24h after the microinjection of haloperidol and 60min after the injection of lidocaine. In rats rendered hemiparkinsionian by lesioning the nigrostriatal pathway with 6OHDA, intrastriatal microinjection of flunarizine (50nmol/microl) significantly reduced apomorphine (0.2mg/kg, s.c.)-elicited turning behavior towards the non-lesioned side. These results suggest an antidopaminergic effect of flunarizine mediated by antagonistic action of post-synaptic striatal dopamine receptors. However, an action of the drug on sodium channels may not be ruled out. These studies offer additional supporting evidence for the induction or aggravation of extrapyramidal side-effects in patients receiving flunarizine.

Topics: 3,4-Dihydroxyphenylacetic Acid; Animals; Apomorphine; Calcium Channel Blockers; Calcium Channels, L-Type; Dopamine; Dopamine Agonists; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Dose-Response Relationship, Drug; Flunarizine; Haloperidol; Male; Microinjections; Neostriatum; Nifedipine; Parkinson Disease, Secondary; Rats; Rats, Sprague-Dawley; Stereotyped Behavior; Synapses; Synaptic Transmission

Topics: Antipsychotic Agents; Catalepsy; Cinnarizine; Drug Design; Flunarizine; Haloperidol; Humans; Parkinson Disease, Secondary; Structure-Activity Relationship; Vasodilator Agents

Cinnarizine (1-diphenylmethyl-4-(3-phenyl-2-propenyl)piperazine) and its di-fluorinated derivative flunarizine inhibit the MgATP-dependent generation of a transmembrane proton electrochemical gradient in chromaffin granule ghosts. The concentrations giving 50% inhibition (IC50) of the MgATP-dependent generation of the pH-gradient were 5.9+/-0.6 microM (n = 6) and 3.0+/-0.3 microM (n = 5) for cinnarizine and flunarizine, respectively. The IC50 values for inhibiting the generation of the membrane potential were even lower, i.e. 0.19+/-0.06 microM (n = 6) and 0.15+/-0.01 microM (n = 4) for cinnarizine and flunarizine, respectively. Cinnarizine (10 microM) also inhibited the energy-dependent vesicular uptake of [14C]-dopamine (50 microM) by 76%, i.e. from 2.1+/-0.9 to 0.5+/-0.6 nmol/mg protein/min (n = 5, P < 0.002). Cinnarizine (10 microM) increased the MgATPase activity of the granule ghosts by 47+/-26% (n = 4) compatible with an uncoupling of the vacuolar H+-ATPase activity. The IC50-values observed for the two compounds are in the same range as their reported therapeutic plasma concentrations in vivo, suggesting that cinnarizine and flunarizine may well inhibit proton pumping and catecholamine uptake in storage vesicles also in vivo. This mechanism of action may contribute to the drug-induced parkinsonism seen as a side-effect of the two drugs.

Topics: Animals; Cattle; Chromaffin Cells; Cinnarizine; Dopamine; Energy Metabolism; Flunarizine; Parkinson Disease, Secondary; Proton-Translocating ATPases; Synaptic Vesicles; Uncoupling Agents; Vacuoles

The aim of the present study is to investigate whether there are geographic differences in the etiology of parkinsonism (PA).. 72% of patients with PA evaluated at movement disorders clinics in the Northern Hemisphere are diagnosed with Parkinson's disease (PD). Data regarding other regions are not available.. We reviewed the charts of all patients with PA seen at the Federal University of Minas Gerais Movement Disorders Clinic from July 1993 through October 1995. PA was diagnosed by the presence of at least two of the following: rest tremor, bradykinesia, rigidity, and postural instability. The different etiologies were diagnosed based on standard clinical criteria.. During the period of the study, PA was recognized in 338 subjects. The following clinical diagnoses were made: PD (68.9%), drug-induced PA (DIP) (13.3%), vascular PA (4.7%), Progressive supranuclear palsy (PSP) (2%), multiple system atrophy (MSA) (1.8%), others (9.7%). Cinnarizine, haloperidol and flunarizine were the commonest drugs related to DIP.. Similarly to other studies, PD accounts for about 70% of PA patients. However, there are differences between our results and previous series. DIP is much more common in the present series. This may be accounted for a more liberal use of antidopaminergic drugs in our environment, especially Calcium channel blockers. The lower frequency of MSA and PSP in our study may reflect a short follow-up, since many patients initially diagnosed with PD later are found to have Parkinson-plus syndromes.

Topics: Aged; Anti-Dyskinesia Agents; Brazil; Calcium Channel Blockers; Cinnarizine; Female; Flunarizine; Haloperidol; Histamine H1 Antagonists; Humans; Male; Middle Aged; Parkinson Disease; Parkinson Disease, Secondary

The natural course of calcium-entry blocker-induced parkinsonism was evaluated in 13 elderly patients previously exposed to cinnarizine or flunarizine or both for a median period of 7 months. Clinical assessments were carried out before drug discontinuation and twice thereafter over a period lasting < or = 7 years. None of the patients showed a full recovery of extrapyramidal signs, indicating that the long-term prognosis of the parkinsonism is less benign than previously reported. Two main patterns of clinical outcome were recognized (i.e., "remittent" and "persistent and not progressive" parkinsonism), whereas the development of a progressive disorder was observed only in one patient. No significant correlation was found between the patterns of outcome and some clinical variables, such as total duration of exposure to cinnarizine and flunarizine, cumulative drug dosages, and age at onset of parkinsonism. There was no significant difference in terms of family history of essential tremor or parkinsonism or both among patients with the two main patterns of clinical course.

Topics: Aged; Calcium Channel Blockers; Cardiovascular Diseases; Cinnarizine; Dose-Response Relationship, Drug; Female; Flunarizine; Follow-Up Studies; Humans; Male; Middle Aged; Neurologic Examination; Parkinson Disease, Secondary; Treatment Outcome

Potentialities of cinnarizine [1-(diphenylmethyl)-4-(3-phenyl-2-propenyl)piperazine, CZ] and its fluorine derivative flunarizine [1-[bis(4-fluorophenyl)-methyl]-4-(3-phenyl-2-propenyl)piperazine, FZ] to induce parkinsonism as an adverse effect were evaluated pharmacokinetically and pharmacodynamically in rats. In multiple-dose experiments, CZ or FZ was given to rats at a daily dose of 20 mumol/kg for 1, 5, 10, 15, and 30 days, and CZ, FZ, and the ring-hydroxylated metabolites of their cinnamyl moiety [1-(diphenylmethyl)-4-[3-(4'-hydroxyphenyl)-2-propenyl]piperazine, C-2 and 1-[bis(4-fluorophenyl)methyl]-4-[3-(4'- hydroxyphenyl)propenyl]piperazine, F-2] in the plasma and striatum were determined 24 hr after the final dose. Plasma and striatum concentrations of the above compounds except for FZ reached steady state after 10 doses, but their concentrations of FZ continued to increase throughout the experiments. The concentrations obtained after the 30 doses were in the order of FZ > F-2 > CZ > C-2 for the plasma and of F-2 > FZ > CZ > C-2 for the striatum. The ratios of striatum to plasma concentrations of C-2 and F-2 were 2.4 and 3 times higher than those of the parent drugs. Binding affinities of CZ, FZ, and their 10 metabolites for rat striatal dopamine D-2 receptors (D2-R) were assessed by competitive radioligand-binding studies using [3H]-N-[(2RS,3RS)-1-benzyl-2-methyl-3-pyrrolidinyl]-5-chloro-2-met hoxy- 4-methylamino-benzamide ([3H]-YM-09151-2). The IC50s calculated from their Ki values were in the order of F-2 < C-2 < FZ < CZ < C-4 << F-1, indicating that C-2 and F-2 exhibit higher affinities for D2-R than the parent drugs, whereas affinities of other metabolites were 1 to 2 orders of magnitude less than those of C-2 and F-2. These results suggest some important roles of C-2 and F-2 in the development of parkinsonism as active metabolites during chronic medication with CZ and FZ, respectively.

Topics: Animals; Benzamides; Calcium Channel Blockers; Chromatography, High Pressure Liquid; Cinnarizine; Corpus Striatum; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Drug Administration Schedule; Female; Flunarizine; Parkinson Disease, Secondary; Rats; Rats, Wistar; Receptors, Dopamine D2; Tritium

Topics: Flunarizine; Humans; Parkinson Disease, Secondary; Vasodilator Agents

Cinnarizine and flunarizine are piperazine derivatives with calcium antagonist and anticonvulsant properties and are used widely in the treatment of vertigo and circulatory disorders. They have been implicated recently in the aggravation, or even the induction, of parkinsonism in elderly patients. Because the aetiology of parkinsonism has been suggested as having a mitochondrial component, we have investigated the effects of both compounds on mitochondrial respiration and on the activities of the individual respiratory chain complexes. In intact mitochondria from rat liver, both drugs inhibited respiration rates, with substrates entering at Complex I (glutamate/malate) and Complex II (succinate). These effects could be explained by potent inhibitions (Ki 3-10 microM) of both complexes. Complex I is inhibited at a site near the ubiquinone-binding site, which is not competitive with respect to ubiquinone, whereas the inhibition of Complex II is apparently caused by competition with ubiquinone. Furthermore, the inhibition of NADH oxidation by flunarizine in submitochondrial particles caused an NADH-dependent generation of superoxide. These inhibitory properties of both compounds could be significant factors in the aggravation or induction of parkinsonism in elderly patients, in whom mitochondrial function already may be impaired.

Topics: Animals; Cinnarizine; Electron Transport; Electron Transport Complex II; Flunarizine; Mitochondria, Heart; Mitochondria, Liver; Multienzyme Complexes; NAD(P)H Dehydrogenase (Quinone); Oxidoreductases; Parkinson Disease, Secondary; Rats; Submitochondrial Particles; Succinate Dehydrogenase

Topics: Animals; Flunarizine; Humans; Parkinson Disease, Secondary; Tremor

The risk of developing drug-induced parkinsonism (DIP) has been related to a number of factors but it remains up to now poorly defined. The aim of this survey has been to evaluate retrospectively the possible role of inherited components in 25 patients with parkinsonism induced by chronic exposure to the calcium-entry blockers cinnarizine and flunarizine. The finding of higher occurrence of a positive family history for Parkinson's disease (PD) and/or essential tremor (ET) and of higher frequency of secondary cases with PD and/or ET among close relatives of the patients as compared to age-matched controls, suggests the involvement of genetic susceptibility in developing this drug-induced disorder. DIP could be regarded as a multifactorial disease process resulting from potential neurotoxicity of drugs on a background of inherited predisposition.

Topics: Aged; Aged, 80 and over; Calcium Channel Blockers; Cinnarizine; Disease Susceptibility; Female; Flunarizine; Humans; Male; Middle Aged; Parkinson Disease, Secondary; Retrospective Studies; Risk Factors

Flunarizine hydrochloride (FZ) is used to improve cerebral circulation and possesses Ca antagonistic effects. In recent years, this drug has been reported to induce parkinsonism and depressive symptoms as side effects, particularly in the elderly. Effects of FZ on dopamine receptors of the rat striatum were studied by radiolabeled receptor assay to clarify the mechanism of onset of parkinsonism in response to FZ. FZ was found to directly and competitively affect D-2 receptors without affecting D-1 receptors. Furthermore, the effect of FZ on D-2 receptors was found to be antagonistic based on the finding that the displacement curve for FZ in the binding of [3H]spiperone to D-2 receptors remained unchanged even after the addition of GppNHp. The effect of FZ on the D-2 receptors in aged rats was more marked than that in young-adult rats. In addition, the tertiary structures of FZ and the anti-schizophrenic agents, pimozide and haloperidol, were examined using computer graphics. FZ was found to have a tertiary structure highly analogous to pimozide and haloperidol, and FZ also had an alkyl structure linking a fluorophenyl group and a nitrogen atom, believed to be particularly necessary for the binding of anti-schizophrenic agents to D-2 receptors. These results may contribute to clarifying the mechanism of onset of parkinsonism in response to FZ, especially in the elderly.

Topics: Age Factors; Animals; Corpus Striatum; Dopamine Antagonists; Flunarizine; Male; Molecular Structure; Parkinson Disease, Secondary; Rats; Rats, Inbred Strains; Receptors, Dopamine D2

When controversy suddenly erupts about the risk of using a prescription drug, there is an urgent need for fast methods of risk estimation. Some unexpected side-effects of prescription drugs are indications for the prescribing of another kind of drug. If the risk of such a side-effect is high, it should be reflected in clustered prescribing of the side-effect-alleviating drug in sequence with the side-effect-causing drug. The risk of drug-attributable side-effects can be estimated by comparing average incidences of initial prescriptions for the side-effect-alleviating drug before, during, and long after the dispensing of the presumed side-effect-causing drug. We monitored computerized, complete drug dispensing records of anonymous outpatients for use of flunarizine, an anti-vertigo/anti-migraine drug that case reports had suggested causes mental depression and/or Parkinsonism. Among 1284 patients who eventually got flunarizine during a 31 month period, 1 in 7 was started on an anti-depressant before or long after flunarizine; only 1 in 82 might be said to have been started on an anti-depressant because of flunarizine. There was no evidence that anti-Parkinson drugs were started because of flunarizine, though the numbers are small. The analysis takes only a few days, and can help set bounds on risks of the subset of adverse drug reactions that are themselves indications for use of other drugs.

Topics: Aged; Antidepressive Agents; Antiparkinson Agents; Depression; Drug Prescriptions; Female; Flunarizine; Humans; Incidence; Male; Middle Aged; Parkinson Disease, Secondary; Pharmacies; Risk Factors; Time Factors

Topics: Aged; Anemia; Cognition Disorders; Consciousness Disorders; Drug Interactions; Flunarizine; gamma-Aminobutyric Acid; Humans; Intestinal Absorption; Pantothenic Acid; Parasympatholytics; Parkinson Disease, Secondary; Psychotropic Drugs; Reye Syndrome

Flunarizine hydrochloride (FZ), a calcium entry blockade, has been used nationwide in Japan as a cerebral active vasodilator since October, 1984. The present paper reports 31 cases of FZ-induced Parkinsonism, depression and akathisia, referred to our hospital between October 1986 and September 1988. Out of the 31 patients, four including two with Parkinson's disease and one each with progressive supranuclear palsy and olivopontocerebellar atrophy showed worsening of their parkinsonian symptoms within a few months after FZ administration. The remaining 27 patients (7 males and 20 females) newly developed Parkinsonism after treatment with FZ. Symptoms appeared one week to two years (mean: 6.1 months) after starting FZ of a daily dose of 10 mg. FZ had been used in 6 patients for cerebrovascular episodes confirmed by clinical history or brain CT, and in the remainder, for dizziness, light-headedness, hypertension, amnesia or hypochondric neurotic complaints. Akinesia and bradykinesia progressed rather rapidly after onset, and patients became unambulatory within several months. Symptoms had worsened, and L-dopa, anticholinergic drugs, and bromocriptine had been ineffective until FZ was discontinued. Their Parkinsonism was characterized by marked akinesia, bradykinesia, and moderate rigidity. Masked face was seen in most of them. Tremor was absent at rest, and induced in 12 patients by posture and/or action. Sixteen patients were accompanied by depression, and five, by akathisia. Improvement began several weeks after withdrawal of FZ, and most patients recovered almost completely within a few months although mild rigidity and bradykinesia remained in some.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Aged, 80 and over; Akathisia, Drug-Induced; Depression; Female; Flunarizine; Humans; Male; Middle Aged; Parkinson Disease, Secondary

The author describes the cases of eight patients with severe Parkinson syndrome who had their symptoms vanished after suspension of flunarizine, except for one case whose symptoms remitted partially. The author intention is clearly to alert to this unfavorable reaction, since there may be a lot of patients treated like having Parkinson disease in use of flunarizine.

Topics: Aged; Female; Flunarizine; Humans; Middle Aged; Parkinson Disease, Secondary

The authors studied 19 patients with parkinsonism induced by flunarizine. All them improved when the drug therapy was discontinued for periods from 7 days to 10 months. Depression was observed in 68.5% of the patients.

Topics: Adult; Aged; Female; Flunarizine; Humans; Male; Middle Aged; Parkinson Disease, Secondary

Over the last few years, cases of movement disorders induced by flunarizine and cinnarizine have been increasingly reported. We describe a series of 101 patients, whose ages ranged from 37 to 84 years (mean 69.1), developing abnormal movements frequently associated with depression, secondary to treatment with either or both drugs. Symptoms closely resembled those induced by neuroleptic drugs and remitted on drug discontinuance in all but five cases after 5-22 months' follow-up. Whether or not such undesirable side effects are attributable to calcium antagonism and/or dopamine receptor blockade, long-term treatment with flunarizine or cinnarizine should be discouraged, particularly in the elderly.

Topics: Adult; Aged; Aged, 80 and over; Basal Ganglia Diseases; Cinnarizine; Depression; Dyskinesia, Drug-Induced; Dystonia; Female; Flunarizine; Humans; Male; Middle Aged; Parkinson Disease, Secondary; Tremor

Topics: Adult; Aged; Cinnarizine; Depression; Female; Flunarizine; Humans; Male; Middle Aged; Parkinson Disease, Secondary; Time Factors; Tremor

Twenty-seven patients (19 women and 8 men, ages 63 to 88 years; mean, 74 years) displayed mild to moderate parkinsonism and altered ballistic motor performances during long-term flunarizine treatment. One month after, flunarizine withdrawal, 20 patients showed clear-cut improvements in both clinical features and ballistic motor performances; a complete recovery within 6 months was observed in all these patients but one, who still showed very mild slowness of movement. On the other hand, seven patients showed little clinical improvement and still maintained markedly altered ballistic motor performances 1 month after drug withdrawal. At the 2-month follow-up assessments, either they did not improve further or they deteriorated; they were successfully treated with L-dopa and, despite the ameliorations, after 12 to 24 months they still have definite parkinsonian syndrome. The authors conclude that (1) flunarizine, even at the recommended dose (10 mg daily), can induce reversible parkinsonism, at least in subjects older than 60; (2) the persistence of a marked symptomatology 2 months after flunarizine withdrawal should lead to starting treatment with antiparkinsonism drugs; (3) the study of ballistic movements is proposed as a useful tool for objective quantification and early detection of bradykinesia.

Topics: Aged; Aged, 80 and over; Electromyography; Female; Flunarizine; Humans; Male; Middle Aged; Parkinson Disease, Secondary

Topics: Animals; Caudate Nucleus; Cinnarizine; Dopamine; Flunarizine; Male; Nifedipine; Parkinson Disease, Secondary; Rats; Rats, Inbred Strains; Receptors, Dopamine

We consider 24 cases of iatrogenic parkinsonism related to flunarizine, evaluating the clinical features of the syndrome and the improvement following withdrawal.

Topics: Aged; Aged, 80 and over; Calcium Channel Blockers; Female; Flunarizine; Humans; Male; Middle Aged; Parkinson Disease, Secondary; Time Factors

Cinnarizine and flunarizine are selective calcium blockers that have been used to treat and prevent vertigo. We studied 15 patients who had extrapyramidal syndromes after taking these drugs. Eleven patients had parkinsonism, one with persistent akathisia as well; one had an orofacial tremor; one, acute akathisia alone; and one an acute dystonic reaction. All but one improved when the drug therapy was discontinued. Seven patients were also depressed during treatment. Cinnarizine and flunarizine must therefore be added to the list of potentially risky drugs known to induce extrapyramidal reactions and depression.

Topics: Adult; Aged; Aged, 80 and over; Brain Diseases; Cinnarizine; Female; Flunarizine; Humans; Male; Middle Aged; Movement Disorders; Parkinson Disease, Secondary; Pyramidal Tracts

Topics: Aged; Female; Flunarizine; Humans; Male; Middle Aged; Movement Disorders; Muscle Rigidity; Parkinson Disease, Secondary

12 subjects, 8 women and 4 men, presented with extrapyramidal motor signs and psychic depression after treatment with flunarizine for between 3 weeks and 15 months. One woman presented with severe symptoms and 20 months after stopping flunarizine she still had dyskinesia and akathisia. The other patients showed partial or complete improvement after withdrawal of the drug.

Topics: Aged; Akathisia, Drug-Induced; Cinnarizine; Depressive Disorder; Dyskinesia, Drug-Induced; Female; Flunarizine; Humans; Male; Middle Aged; Parkinson Disease, Secondary; Psychoses, Substance-Induced