Conditioned physiological adaptation to anticholinergic drugs

Abstract

In conscious, unrestrained dogs, multiple intravenous treatments with equivalent doses of atropine sulfate and atropine methyl nitrate produced conditioned responses of paradoxical salivation and classical mydriasis with comparable onset, peak effects, and extinction rates. Since atropine methyl nitrate does not readily enter the central nervous system, these conditioned responses are the result of peripheral anticholinergic drug actions. Pretreatment with the alpha adrenergic blocker, phenoxybenzamine, selectively inhibited the mydriatic response, whereas administration of propranolol, abetaadrenergic blocker, preferentially inhibited the conditioned salivation. The salivary and mydriatic responses resulted from conditioned physiological adaptation mediated through a central sympathetic reflex and with efferent alpha and beta adrenergic pathways.