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Original article:-Pharmacology
Chandel Nitibhushansingh R1, Phadke Anant G2 and Goyal Chhaya A3
1M.D. (Pharmacology), Assistant Professor, 3M.D( Pharmacology), Professor, Department of Pharmacology, SAIMS Medical College & PG Institute, Indore, Madhya Pradesh, India. 2M.D.(Pharmacology), Professor, Department of Pharmacology, JNMC, Sawangi (Meghe), Wardha, India.
Abstract:- Aim: To study the interaction of calcium channel blocker (verapamil) with Antipsychotic drug (Haloperidol) in CAR and catalepsy models in rats.
Methods and Results: Every group consisted of 10 healthy albino rats of either sex. Different groups received Verapamil (5, 10 &20 mg/kg, i.p.), Haloperidol (ED50 -0.2mg/kg) alone and combined doses of both drugs. The Antipsychotic effect of drugs was measured by Conditioned avoidance response (CAR) using Cook’s Pole climbing apparatus and Adverse drug effect (Extra pyramidal syndrome) was measured by Catalepsy. 5 mg/kg i.p. of Verapamil inhibited CAR in 50 % of Rats (compared to control, p<0.001). 10mg/kg i.p. of verapamil inhibited CAR in 70% of Rats (p<0.001) & 20 mg/kg i.p. inhibited CAR in 80% of Rats (p<0.001). When verapamil (5 mg/kg i.p) was combined with Haloperidol ED50-0.2mg/kg the CAR was inhibited in 80% of the rats (p<0.001) and after combining verapamil (10mg/kg) with Haloperidol ED50-0.2mg/kg the CAR was inhibited in 100% Rats. (p<0.001) Verapamil at the dose of 5 mg/kg and 10 mg/kg (i.p.) did not induce catalepsy in the rats at any testing time interval. At 20 mg/kg i.p., it produced catalepsy in 3 rats at half hour and in 5 rats at 1 hour and 2 hour testing interval each.(p<0.01). Verapamil pretreatment in the dose of 5 mg/kg did not affect the haloperidol (ED50 -0.4 mg/kg) induced catalepsy. In the dose of 10 and 20 mg/kg, pretreatment with verapamil significantly increased cataleptic scores at all testing intervals (P<0.05).Conclusion: Verapamil blocked CAR. Its higher doses induced catalepsy and it is synergistic with haloperidol in blockade of CAR and catalepsy.
Key words:- Verapamil, Haloperidol, Conditioned avoidance response (CAR), Catalepsy.