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1 Department of Pharmacology, Harvard Medical School, Boston, Massachusetts
Nicotinic and muscarinic agonists (1,1-dimethyl-4-phenylpiperazinium, tetramethylammonium, amyltrimethylammonium, hexyltrimethylammonium, pilocarpine, McNeil A-343 [4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium chloride)] were injected i.a. into cardiac ganglia of spinal dogs. Heart rate was used as an indicator of ganglionic stimulation. All agents possessed potent and powerful ganglionic stimulant activity. Small doses of nicotinic antagonists (hexamethonium, d-tubocurarine, tetraethylammonium and mecamylamine) increased the maximally obtainable response to all agonists except amyl- and hexyltrimethylammonium. Larger doses of the antagonists shifted the dose-response curves to nicotinic agonists stepwise to the right. Atropine had the same effect on muscarinic agonists. Amyl- and hexyltrimethylammonium had both nicotinic and muscarinic activity. The pA plot for both types of agent groups was suggestive of interaction at a single receptor. Thus, the experiments provide evidence that these ganglia contain two separate types of cholinergic receptors, and perhaps, an additional inhibitory one.
Submitted on June 25, 1969