flunarizine and Parkinson-Disease

Flunarizine and cinnarizine have been well documented to cause EPS. Other CCBs, on rare occasions, also have been reported to cause EPS. Theoretical explanations for these events include the inhibition of calcium influx into striatal cells and direct dopaminergic antagonistic properties. In addition, the chemical structures of flunarizine and cinnarizine, which are related to neuroleptics, may explain the relatively greater incidence of EPS with these agents. Suggested risk factors for acquiring EPS with flunarizine or cinnarizine use appear to be age, although experience with using these agents in younger patients is limited, and a family history of tremors and/or Parkinson's disease. The onset and type of presentation is unpredictable and, in most instances, discontinuation of the medication relieves the symptoms within a few days to months. Pharmacologic management of EPS with continued use of the offending agent generally has not been of clinical benefit. In conclusion, patients receiving CCBs, particularly flunarizine and cinnarizine, should be monitored for EPS.

Topics: Basal Ganglia Diseases; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Flunarizine; Humans; Parkinson Disease; 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

Embryonic nigral grafts can survive, reinnervate the striatum and reverse functional deficits in both experimental and clinical Parkinsonism. A major drawback is that only around 10% of the implanted dopaminergic neurons survive. The underlying mechanisms leading to this 90% cell death are not fully understood, but oxidative stress and a substantial loss of neurotrophic support are likely to be involved. Hypoxia and mechanical trauma, which are unavoidable during tissue preparation, may be a trigger for cell death. Recent studies have provided evidence that the type of cell death occurring is, to a large extent, apoptotic. Flunarizine is an antagonist of L-, T- and N-type calcium channels, which permits calcium entry into cells via a voltage-dependent mechanism. Flunarizine has been shown to protect neurons against death induced by serum deprivation, nerve growth factor deprivation, oxidative stress, axotomy and ischemia. This study was designed to investigate whether flunarizine can protect grafted embryonic dopaminergic neurons from death when implanted in a rat model of Parkinson's disease. Addition of 1 microM flunarizine inhibited cell death in a suspension of cells derived from the rat's ventral mesencephalon and when such a treated suspension was injected into the neostriatum there was a 2.6-fold greater number of surviving dopaminergic neurons, a doubling of the graft volume and a doubling of the volume of the host neostriatum innervated by dopaminergic fibers from the graft, compared with suspensions not exposed to flunarizine. Furthermore, rats injected with cells that had been exposed to flunarizine displayed a greater recovery of function in the amphetamine-induced rotation test.

Topics: Animals; Apoptosis; Brain Tissue Transplantation; Calcium; Calcium Channel Blockers; Calcium Channels; Cell Survival; Dopamine; Female; Fetal Tissue Transplantation; Flunarizine; Graft Survival; Neurons; Oxidative Stress; Parkinson Disease; Rats; Rats, Sprague-Dawley; Substantia Nigra

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

Twenty-six patients under treatment with the calcium channel blockers flunarizine (Fz) or cinnarizine (Cz) were examined-with single-photon emission computed tomography using [123I]iodobenzamide as a ligand. The striatal dopamine D2 receptor-binding potential was determined and found to be reduced by 14 to 63% (39.5 +/- 15.0%; p < 0.0001) in patients compared with age-matched control values. This reduction was larger in 12 patients with extrapyramidal symptoms and was only slowly reversible after discontinuation of treatment. Patients treated for > 6 months had significantly larger reductions than patients treated for a shorter period. Parkinsonian symptoms were only seen in patients older than 50 years. Our findings prove a neuroleptic-like action of Fz and Cz, which seems to be the major reason for their extrapyramidal side effects. Older age and long-term treatment are predisposing factors for these effects.

Topics: Adult; Aged; Brain Diseases; Cinnarizine; Dopamine D2 Receptor Antagonists; Female; Flunarizine; Humans; Male; Middle Aged; Parkinson Disease; Tomography, Emission-Computed, Single-Photon

In rats with a unilateral lesion of the nigrostriatal dopaminergic pathway, the ipsilateral rotation produced by the enhanced actions of endogenous dopamine (DA) on the nonlesioned side, induced by either the DA-releasing drug amphetamine or the DA uptake inhibitor GBR 13069, was blocked effectively by pretreatment with either the selective D1 DA receptor antagonist, SCH 23390, or the D2 selective antagonist, haloperidol. In contrast, contralateral rotation produced by apomorphine or I-dihydroxyphenylalanine, which lead to the preferential activation of D1 and D2 receptors on the lesioned side, was effectively prevented only when both receptor subtypes were inhibited. The results of these experiments demonstrate that the interaction between D1 and D2 receptors in the lesioned side differs from that in the nonlesioned side. Whereas the simultaneous stimulation of both DA receptor subtypes in the normally innervated basal ganglia is required for the production of turning behavior, the stimulation of either subtype alone in the dopaminergic denervated side can produce rotation. However, the concurrent administration of the D1 agonist, SKF 38393, with the D2 agonist, LY 171555, produced a synergistic effect on contralateral rotation. These results suggest that there is preservation of at least some functional interaction between D1 and D2 receptors in the lesioned basal ganglia but that there may be in addition a mechanism by which the two receptor subtypes can function independently of each other. The unilaterally lesioned rat appears to be a very good model in which to study the interaction between D1 and D2 receptors under conditions of both normal innervation and of DA denervation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Animals; Basal Ganglia; Benzazepines; Corpus Striatum; Denervation; Dextroamphetamine; Ergolines; Female; Flunarizine; Functional Laterality; Haloperidol; Levodopa; Neural Pathways; Parkinson Disease; Quinpirole; Rats; Rats, Inbred Strains; Receptors, Dopamine; Receptors, Dopamine D1; Receptors, Dopamine D2; Rotation; Substantia Nigra