Hypersensitivity of cardiac muscarinic receptors during sodium barbital tolerance and withdrawal

Abstract

Rats when administered with sodium barbital (150 mg kg -1 , i.p., 12 hourly) for 5 to 25 days developed tolerance to the compound. These barbital-treated rats compared to the control saline-treated rats, exhibited significantly greater negative chronotropism to pilocarpine on days 5, 15, and 25 of the treatment. The observed hypersensitivity of cardiac muscarinic receptors to pilocarpine decreased gradually and returned to normalcy within 10 days after the cessation of the treatment i.e. on day 15. Though the order of potency of cholinergic agonists in producing negative chronotropism in the control rats was carbachol > methacholine > pilocarpine, the chronotropic action of carbachol in the 15 day barbital-treated rats was least affected. On the other hand the chronotropic action of pilocarpine in the latter animals was greatly enhanced.