PHARMACOLOGIC AND TOXICOLOGIC STUDIES OF m-(1-METHYL-3-PROPYL-3-PYRROLIDINYL)PHENOL (CI-572), AN ANALGETIC AND ANTITUSSIVE AGENT

¹ Department of Pharmacology, Research Division, Parke, Davis & Company, Ann Arbor, Michigan

CI-572 has a considerably greater, nalorphine-antagonized antinociceptive activity in rats (2.5-4 times codeine or meperidine) than prodilidine, and, unlike prodilidine, has a corresponding antitussive activity in dogs with ammonia-induced cough. Yet, like prodilidune, it fails to alleviate morphine abstinence signs in monkeys. It resembles prodilidine in lacking antiultraviolet erythema action in guinea pigs and antipyretic action in rats. It equals or exceeds prodilidune as an excitant in toxic doses in rodents and monkeys. It differs from prodilidine because it raises body temperature in rats and because it is transiently constipating in rats. Its l-isomer is twice as potent and toxic as the d-isomer. CI-572 is somewhat less potent orally than subcutaneously when compared with codeine or meperidine, whereas prodilidine is more effective orally than subcutaneously. The ratio of potency to acute sublethal or lethal toxicity in rats was generally higher with CI-5fl than with codeine or meperidine. Subacute oral toxicologic studies in rats, dogs and monkeys indicated that organic pathology occurred only at daily dose levels which exceeded those zig-naling neuromotor discomfort several times.