A STUDY OF SYMPATHETIC GANGLIONIC STIMULANTS

¹ Department of Pharmacology, Medical College of Georgia, Augusta, Georgia

Two categories of agents that produce adrenergic effects by ganglion stimulation have been compared. The action of category I agents, represented by dimethylphenylpiperazinium iodide (DMPP) is potentiated by atropine and blocked by ganglion blocking agents. The action of category II agents, represented by 4-(m-chlorophenylcarbamoyloxy) -2- butynyltrimethylammonium chloride (McN-A-343), is potentiated by ganglionic blocking agents and blocked by small doses of atropine. Pilocarpine, neostigmine and edrophonium can be classified as category II ganglion stimulants since they produce adrenergic effects after ganglionic blocking agents, and these adrenergic effects are blocked by atropine. The principal adrenergic effects studied were the pressor response, the positive chronotropic response and intestinal inhibition.

Methylphenidate reduced or abolished the adrenergic responses produced by the agents in category II. The adrenergic responses to DMPP were either not reduced or were augmented. Since the adrenergic responses to tyramine were also reduced it is probable that the site of action of methylphenidate is at or near the peripheral adrenergic neurone.

Guanethidine duplicated the effects of methylphenidate pretreatment with the exception that the pressor response to tyramine was not reduced by acute treatment with guanethidine, but was abolished 24 hours after pretreatment with guanethidine.

Pheniprazine, amphetamine and hydroxyamphetamine reduced or abolished the adrenergic responses to agents in category II and did not reduce (but possibly augmented) these pressor responses to DMPP. This blocking effect was prevented by pretreatment with morphine. The pressor response to tyramine was increased by these agents. Iproniazid did not alter the actions of either category of ganglionic stimulants.

HC-3 (hemicholinium) did not reduce the pressor responses to agents of either category. Win-4981 [3,6-bis(3-diethylaminopropoxy) pyridazine bis-methiodide] pretreatment specifically prevented the pressor response to neostigmine but did not affect the response to any other agent in either category I or II.

P-286 (N,N-diisopropyl-N'-isoamyl-N'-diethylaminoethylurea HCl) reduced or abolished the pressor responses to all agents in both categories. The depressor responses to McN-A-343 and pilocarpine were still present after P-286 treatment and were abolished (as were those of muscarine) by atropine. This suggested a stimulant effect of McN-A-343 on peripheral cholinergic receptor sites. The proposed site of action of P-286 is at the ganglion level.