cinnarizine and Parkinsonian-Disorders

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

This retrospective cohort study used a population-based dataset to test the risk for parkinsonism in patients receiving flunarizine and cinnarizine, compared with matched controls.. Data were obtained from the National Health Insurance Research Dataset of Taiwan. Patients receiving flunarizine or cinnarizine for more than 1 month between 2000 and 2005 were enrolled. Exclusion criteria included receiving flunarizine, cinnarizine, or antipsychotics for more than 1 month during 1997-1999, a history of neurodegenerative diseases, and an age of less than 30 years. One matched control for each patient was selected. Each participant was followed for diagnosis of parkinsonism within a 3-year observation period. Stroke, diabetes mellitus, total prescription days, and doses of flunarizine or cinnarizine were recorded.. The study and control groups consisted of 9830 subjects. In the study group, 280 patients (2.9 %) were diagnosed with parkinsonism with a median observation period of 1.2 years, and 49 participants (0.5 %) were diagnosed in the control group with a median observation period of 1.9 years. The adjusted hazard ratio for parkinsonism among patients receiving flunarizine and cinnarizine was 5.117 (95 % CI = 3.758-6.967). Age, stroke, and diabetes mellitus were significant risk factors, but female sex and total doses of the study drugs were not.. This study demonstrates that flunarizine and cinnarizine significantly increase the risk for parkinsonism. The treatment benefits of these two agents should be balanced with this adverse effect. Physicians must look carefully for early signs of parkinsonism in patients treated with flunarizine and cinnarizine.

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Cinnarizine; Female; Flunarizine; Humans; Male; Middle Aged; Parkinsonian Disorders; Retrospective Studies; Risk Factors

We performed a clinical report based, descriptive and retrospective study, aimed at comparing Flunarizine/Cinnarizine-induced parkinsonism (FCIP) patients and Parkinson's disease (PD) patients. The FCIP group (n = 30) presented a lower frequency of rigidity and unilateral tremor than the PD group (n = 70). All FCIP patients improved, 13 after dopaminergic treatment. FCIP patients who improved spontaneously presented lower frequency of rigidity, compared with the other FCIP subgroup and PD group. FCIP patients who did not improve spontaneously showed a clinical pattern similar to PD patients.

Topics: Aged; Aged, 80 and over; Calcium Channel Blockers; Cinnarizine; Dopamine Agonists; Female; Flunarizine; Humans; Male; Middle Aged; Muscle Rigidity; Parkinson Disease; Parkinsonian Disorders; Retrospective Studies; Statistics, Nonparametric; Treatment Outcome; Tremor

To investigate the etiologic diagnoses of parkinsonism, underlining aspects of each form and comparing our findings with those published in a similar setting, 10 years before.. A large cohort of 1528 patients with parkinsonism was analyzed, gathering data on demography, motor and non-motor characteristics, as well as the final etiologic diagnoses based on established criteria.. Parkinson's disease (PD) was the most common diagnosis representing 74.7%, followed by drug-induced parkinsonism (DIP) in 7.9%, vascular parkinsonism (VP) in 3.9%, other neurodegenerative disorders in 10%, and rare sporadic causes, divided as genetic, infectious and others, that summed 3.5%. Comparative analysis of these groups showed that each has particularities that extend beyond their diagnostic criteria.. The main conclusions are that the most important causes of parkinsonism in this setting are typical, with PD been the most common diagnosis, although other causes were frequent, encompassing one fourth of all cases. Although DIP was identified in a particularly large part of this cohort, this proportion is smaller than demonstrated previously in a Brazilian study conducted in the 90s. This decrease probably reflects higher awareness regarding the risk of this motor complication and the more widely used newer antipsychotics.

Topics: Aged; Antipsychotic Agents; Cinnarizine; Cohort Studies; Diagnosis, Differential; Female; Flunarizine; Haloperidol; Humans; Male; Methotrimeprazine; Movement Disorders; Outpatient Clinics, Hospital; Parkinsonian Disorders; Psychotic Disorders; Risperidone; Severity of Illness Index; Time Factors; Valproic Acid

Topics: Aged; Calcium Channel Blockers; Cinnarizine; Female; Flunarizine; Humans; Parkinsonian Disorders

Cinnarizine, a calcium antagonist that produces parkinsonism in humans, induces behavioural changes such as alopecia, buco-lingual dyskinesia and reduction of motor activity in female parkin knock out (PK-KO) mice but not in wild-type (WT) controls. PK-KO mice have high striatal dopamine levels and increased dopamine metabolism in spite of low reduced tyrosine hydroxylase protein. Cinnarizine, which blocks dopamine receptors and increases dopamine release, further increased dopamine metabolism. PK-KO mice increased GSH levels as a compensatory mechanism against enhanced free radical production related to acceleration of dopamine turnover. Neuronal markers, such as beta-tubulin slightly increased in PK-KO and furthermore with cinnarizine. Astroglial markers were decreased in PK-KO mice, and this effect was potentiated by cinnarizine, suggesting abnormal glia in these animals. Microglia was hyperactivated in PK-KO midbrain, suggesting inflammation in these animals. Proapoptotic proteins were increased by cinnarizine and, to a lesser extent, in PK-KO mice. Our data indicate that mutation of parkin is a risk factor for drug-induced parkinsonism.

Topics: Analysis of Variance; Animals; Antigens, Differentiation; bcl-2-Associated X Protein; bcl-X Protein; Behavior, Animal; Biogenic Monoamines; Blotting, Western; Body Weight; Brain Chemistry; Calcium Channel Blockers; Chromatography; Cinnarizine; Drinking; Eating; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Glutathione; Humans; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Activity; Parkinsonian Disorders; Proto-Oncogene Proteins c-bcl-2; Tyrosine 3-Monooxygenase; Ubiquitin-Protein Ligases

The purpose of this study is to determine the prevalence and the patterns of movement disorders (MD) in outpatients submitted to the chronic use of cinnarizine (cz) or flunarizine (fz), and to establish the main risk factors for MD development. Over a period of 3 months, data were collected from outpatients who were chronic users of cz or fz in a municipal health institute. A total of 26 outpatients were included and all of them were submitted to a protocol that included DSM-4 diagnosis criteria for drug-induced movement disorders, parkinsonism (PK) and depression. Parkinsonism was diagnosed in 34% of the patients, PK plus akathisia, PK plus akathisia and bucco-linguo-masticatory syndrome (BLMS), isolated BLMS and dystonia were found in 4% patients each. Patients with BLMS had the highest median age and the longest average period in which they used the drugs. The affected group, when compared to the non-affected one, presented with higher rates of depression. This study demonstrates the existence of a direct relationship between the time of use of cz and fz, the age and the prevalence of PK and other MD. It also suggests that these drugs increase the incidence of depression.

Topics: Adult; Aged; Aged, 80 and over; Calcium Channel Blockers; Cinnarizine; Depression; Female; Flunarizine; Humans; Male; Middle Aged; Movement Disorders; Parkinsonian Disorders; Retrospective Studies; Risk Factors; Time Factors