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KMID : 0361519940050010019
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Korean Journal of Psychopharmacology
1994 Volume.5 No. 1 p.19 ~ p.34
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Clozapine: A Review of its Pharmacological Properties, therapeutic Efficacy and Adverse Effects
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Abstract
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clozapine, the prototype of an atypical antipsychotic drug. Is a dibenzodiazepine derivative related chemically to loxapine. Clozapine displays antagonistic properties on a variety of CNS receptors. lt is characteristized by weak central
dopaminergic
antagonstic activity relative to the classical antipsychotics. With a different ratio of actions at dopamine D1 and D2 receptors and possibly interaction at the newly described D4 receptor. Other neurotransmitter interactions include antagonism
at
cholinergic. Serotonergic, histaminergic and adrenergic receptors. Neurophysiological and biochemical data indicatethat clozapine has a preferential action on mesolimbic rather than striatal dopaminergic pathways and that this site specificity
may
underlie its atypical extrapyramidal side-effect profile.
Therapeutic effectiveness of clozapine has been found to be superior to placebo and equal or superior to standard antipsychotic drugs in double-blind. Controlled studies. Furthermore. Clozapine is effective in substantial proportion (30 to 60%)
of
schizophrenic patients who are non-responsive or intolernt to classical antipsychotic drug therapy. Clozapine causes a low incidence of extrapyramidal side effects. And there are no reports of its inducing tardive dyskinesia. Adverse effects
include
sedation. Salivation. Orthostatic hypotension. Tachycardia. Constipation. Benign hyperthermia. And seizure. Many of these effects are transient. Clozapine has relatively higher incidence of granulocytopenia and agranulocytosis than other
antipsychotics.
The exact reasons for these unique properties are still unknown although several hypotheses have been proposed.
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