Agonist and Antagonist Actions of Morphinelike Drugs on the Guinea‐pig Isolated Ileum

Substitution of the side-chain attached to the N atom of narcotic analgesic drugs of the morphine, morphinan and benzomorphan series leads to compounds which antagonize the action of the parent compounds; nalorphine and levallorphan, the allyl analogues of morphine and levorphanol, are widely used as " narcotic antagonists."However, these and other analogues also exhibit agonist properties; for example, they may act as analgesics and depress respiration (Eddy, Halbach & Braenden, 1957; Lasagna, De Kornfeld & Pearson, 1964).This dual action of the "narcotic antagonists " has also been observed in isolated tissues.Paton (1957a) showed that morphine and nalorphine are equally effective in depressing the electrically induced contraction of the longitudinal muscle of the guinea- pig ileum, and Gyang, Kosterlitz & Lees (1964) found that the same holds for their inhibitory actions on the peristaltic reflex or the graded reflex contraction of the longitudinal muscle.The experiments presented in this paper were planned to analyse more fully the actions of " narcotic agonists " and " narcotic antagonists " on the guinea-pig ileum.