Modulatory effect of clozapine on levodopa response in parkinson's disease: A preliminary study

Arevalo, Gonzalo J. Gomez; Gershanik, Oscar S.

doi:10.1002/mds.870080317

Cited by 45 publications

(27 citation statements)

References 12 publications

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“…Furthermore, tardive dyskinesia associated with the prolonged use and subsequent withdrawal of conventional antipsychotic agents is suppressed by high doses of clozapine given over extended periods (Shopsin et al 1979;Kane et al 1988). It has also been reported that clozapine has a beneficial effect on tremor in Parkinson's disease patients (Erevalo and Gershanik 1993). Taken together, these findings suggest that the lack of EPS seen with clozapine may be a consequence of the ability of the compound, at least in part, to suppress its own induction of EPS.…”

Section: Introductionsupporting

confidence: 57%

Clozapine inhibits catalepsy induced by olanzapine and loxapine, but prolongs catalepsy induced by SCH 23390 in rats

Kalkman

Neumann

Tricklebank

1997

Naunyn-Schmiedeberg's Arch Pharmacol

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Loxapine (0.3 mg/kg s.c.), olanzapine (10 mg/kg s.c.) and SCH 23390 (R-(+)-chloro-2, 3, 4, 5-tetrahydro-3-methyl-5-phenyl-1-H-3-benzazepine; 1 mg/kg, s.c.), but not clozapine (10 mg/kg, s.c.), induced catalepsy in rats. Co-administration of clozapine (1, 3 and 10 mg/kg s.c.) dose-dependently inhibited loxapine-induced catalepsy. Clozapine (10 mg/kg s.c.) also prevented the induction of catalepsy by olanzapine. In addition, clozapine abolished the catalepsy induced by loxapine when it was administered after the response had fully developed. In contrast, the duration of SCH 23390-induced catalepsy was prolonged by clozapine, indicating that its anti-catalepsy effects against olanzapine and loxapine are unlikely to be caused by muscle relaxation, sedation or stimulation. Since SCH 23390-induced catalepsy is reported to be blocked by scopolamine, dizocilpine (MK-801) or 8-hydroxy-dipropylamino-tetralin, it is unlikely that muscarinic blockade, NMDA ion channel blockade and 5-HT1A receptor agonism, respectively, are involved in clozapine's action, but the mechanism by which clozapine exerts this anti-cataleptic effect remains unknown.

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Section: Introductionsupporting

confidence: 57%

Clozapine inhibits catalepsy induced by olanzapine and loxapine, but prolongs catalepsy induced by SCH 23390 in rats

Kalkman

Neumann

Tricklebank

1997

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Additionally, clozapine has been shown to reduce symptoms of tardive dyskinesia (Safferman et al 1991) and Meige syndrome (Van Putten et al 1990). Recent evidence indicates that clozapine is effective at ameliorating motor dysfunctions in patients with idiopathic Parkinson's disease (Pakkenberg and Pakkenberg 1986;Bernardi and Del Zompo 1990;Fisher et al 1990;Friedman and Lannon 1990;Arevalo and Gershanik 1993). The antiparkinsonian effects of clozapine can occur at doses that are somewhat lower than those used to treat psychotic patients (e.g., 12.5-25 mg; Friedman and Lannon 1990;Arevalo and Gershanik 1993).…”

Section: Introductionmentioning

confidence: 97%

Effects of clozapine, thioridazine, risperidone and haloperidol on behavioral tests related to extrapyramidal motor function

et al. 1997

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Evidence indicates that the antipsychotic drug clozapine has a low propensity for the induction of extrapyramidal motor symptoms, and also that clozapine has therapeutic effects in patients with idiopathic Parkinson's disease. Because tacrine-induced tremulous jaw movements in rats have been suggested as a possible model of extrapyramidal motor dysfunctions, including parkinsonian tremor, the present work was undertaken to investigate the effects of clozapine on tremulous jaw movements. Clozapine decreased tacrine-induced tremulous jaw movements in a dose-related manner, with an ED50 of approximately 3.3 mg/kg. In order to determine the relative potency of this effect compared to other behavioral effects of clozapine, suppression of lever pressing was also studied. Clozapine reduced lever pressing in a dose-related manner, with an ED50 of approximately 5.4 mg/kg. This indicates that clozapine suppressed jaw movements at or below the doses required for suppression of lever pressing. In contrast, the typical antipsychotic drug haloperidol failed to suppress tacrine-induced tremulous jaw movements in doses up to 1.0 mg/kg, which is about 11-fold higher than the ED50 for suppression of lever pressing with that drug. Thioridazine and risperidone also suppressed tremulous jaw movements in roughly the same dose range at which lever pressing was reduced. It is possible that the suppression of tacrine-induced tremulous jaw movements by clozapine in rats is related to the unique behavioral and motor effects of clozapine. The ratio of potencies of these effects (i.e., suppression of tremulous jaw movements versus suppression of lever pressing) could be used as a behavioral procedure for assessing clozapine-like activity in novel compounds.

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“…[17][18][19][20] Interestingly, the ''super off'' phenomenon 21 observed in PD patients with levodopa therapy also improves with CZP as well as parkinsonian tremor and other motor complications and dyskinesias. [22][23][24][25] Regarding the improvement observed in motor function, we cannot establish with certainty if parkinsonian signs were reduced by the action of CZP, withdrawal of neuroleptic drugs, or both at the same time.…”

Section: Discussionmentioning

confidence: 99%

Pilot study with clozapine in patients with HIV-associated psychosis and drug-induced parkinsonism

Lera

Zirulnik

1999

Mov. Disord.

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Clozapine (CZP) is an atypical antipsychotic drug that does not appear to block striatal dopamine receptors. In six patients who met the criteria of HIV‐associated psychosis and who had previously developed moderate parkinsonism as a result of the use of typical neuroleptic agents, CZP was added in an open, rising dose study. Subjects were evaluated at baseline after at least 7 days without neuroleptic drugs and then monthly for 3 months of the experimental treatment using three rating scales: Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI), and motor examination of the Unified Parkinson's Disease Rating Scale (UPDRS). A significant reduction in psychopathology as represented in the BPRS total score (54.2 at baseline versus 23.9 at month 3) and CGI (2 and 8, respectively) was obtained with a mean CZP dose of 27.08 mg/day. Parkinsonism also improved by an average of 76.5% at the end of the study. One patient did not complete the study as a result of a progressive decrease in leukocyte count while on CZP. These preliminary results suggest that the pharmacologic properties of CZP may be of value in the management of HIV‐psychotic patients.

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Modulatory effect of clozapine on levodopa response in parkinson's disease: A preliminary study

Cited by 45 publications

References 12 publications

Clozapine inhibits catalepsy induced by olanzapine and loxapine, but prolongs catalepsy induced by SCH 23390 in rats

Clozapine inhibits catalepsy induced by olanzapine and loxapine, but prolongs catalepsy induced by SCH 23390 in rats

Effects of clozapine, thioridazine, risperidone and haloperidol on behavioral tests related to extrapyramidal motor function

Pilot study with clozapine in patients with HIV-associated psychosis and drug-induced parkinsonism

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