Darakhshan J Haleem, Farhat Batool, Nadia H Khan, Noor Kamil, Obaid Ali, Zafar S Saify, Haleem M A.
Dopamine/Serotonin metabolite ratio and Extrapyramidal effects of Clozapine in rats.
J Coll Physicians Surg Pak Jan ;12(10):588-92.

Objective: To monitor the effects of clozapine, reported to produce fewer extra pyramidal symptoms (EPS), on the striatal 5-hydroxytryptamine (5-HT) and dopamine (DA) metabolism and DA/5-HT metabolite ratio in rats. Design: Clozapine at doses of 2.5, 5.0 and 10.0 mg/kg or saline were injected (i.p.) to locally bred male albino Wistar rats. The animals tested for activity and catalepsy 10 min and 30 min respectively post-injection were decapitated 1 h after injection to collect the striatum for neurochemical analysis. Place and Duration of Study: Department of Biochemistry, Karachi University. Behavorial and neurochemical effects of the drug were monitored acutely. Subjects and Methods: Motor activity was scored in activity boxes. Catalepsy was monitored on an inclined surface. Neurochemical estimations in the striatum were carried out by HPLC-EC. Results: Administration of clozapine at doses of 5.0 and 10.0 mg/kg decreased activity. Catalepsy was produced at a dose of 10.0 mg/kg. The drug at doses of 2.5 and 5.0 mg/kg increased 3,4 dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) concentrations in the striatum. At a dose of 10 mg/kg, HVA increased and DOPAC did not increase. 5-Hydroxyindoleacetic acid (5-HIAA) decreased at a dose of 10 mg/kg. The ratios HVA/5-HIAA and DOPAC/5-HIAA increased dose dependently. Conclusion: Activity of clozapine towards 5-HT receptors be involved in its beneficial therapeutic profile and ability to produce fewer EPS.

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