Effects of cholinomimetics on cocaine-induced hypotension and apneusis at a ventral brainstem cardiorespiratory control site.

The current study was undertaken to evaluate the effects of cholinomimetic drugs on cocaine-induced central cardiorespiratory depression. Cats anesthetized by urethane (2.0 g/kg) were subjected to topical application at the caudal ventrolateral medullary surface (cVMS) of cocaine and two cholinomimetic pretreatment drugs. The following drug regimens were tested: 37 mM cocaine 1) given alone; 2) given 5 min after 2.7 mM carbachol pretreatment; and 3) given 5 min after 3.6 mM physostigmine pretreatment. In 7 of 11 cats, pretreatment with physostigmine decreased the incidence of cocaine-induced apneusis and hypoventilation significantly (p < 0.05); these animals showed no significant change in the mean arterial blood pressure during the 5-min pretreatment before administration of cocaine. In 4 of 11 cats, the physostigmine pretreatment produced a significant decrease in mean arterial blood pressure followed by lethal cardiorespiratory arrest when cocaine was administered. Pretreatment with carbachol resulted in cardiorespiratory responses which were not significantly different from those produced by cocaine alone. In anesthetized cats not exhibiting hypotensive responses to physostigmine, pretreatment may ameliorate cocaine-induced respiratory failure by ventral brainstem control mechanisms.