Abstract

Four analgesic drugs (morphine, levorphan, alphaprodine, dihydrocodeine) and 2 analgesic-antagonists (nalorphine, levallorphan) were studied for their effects on intestinal motility in vitro and in vivo.

In experiments with isolated rabbit and puppy jejunum, responses to each drug were determined, and were shown to be reversible with washout and to vary with drug concentration, with species and with previous exposure of the tissues to the same or different drugs. As a group, the analgesics and antagonists failed to exhibit significant blocking or potentiating action on spasms of isolated intestine induced by barium, histamine, methacholine, serotonin or "bio-dialysate."

Experiments with trained unanesthetized Thiry-Vella loop dogs demonstrated the following: 1) The unanesthetized dog was far more sensitive to intestinal effects of intravenous analgesic drugs than was the acute anesthetized dog preparation or the in vitro preparation and intestinal hypertonicity or spasm was elicited consistently at subsedative and subnauseant dosage by each analgesic studied. 2) Innervated and extrinsically denervated intestinal loops responded similarly to analgesic drugs. 3) Dihydrocodeine and alphaprodine exhibited approximately [unknown] the intestinal spasmogenic potency of morphine. 4) When intestinal responses to analgesic-antagonist drugs were elicited, their nature varied from one animal to another and between innervated and denervated loops. 5) Administration of either the analgesics or the antagonists caused recurrent abnormal motility patterns (" P waves") to appear in recordings from both innervated and denervated loops. 6) Experiments with autonomic agents failed to reveal the cause of the analgesic or antagonist-induced "P waves," but did demonstrate some interesting interactions of the 2 drug groups. 7) Results of antagonism studies with respect to intestinal tone failed to support the concept of critical and constant analgesic-to-antagonist dose ratios. Instead, the absolute amount of antagonist drug necessary for initial prevention or reversal of analgesic-induced intestinal hypertonicity remained remarkably constant, regardless of the particular analgesic drug employed, dose (over a 100-fold range) of analgesic administered or order of administration.