Inhibition of gastrointestinal transit by morphine and FK 33-824 in the rat and comparative narcotic antagonist properties of naloxone and its N-methyl quaternary analog.

Morphine and the enkephalin-like peptide FK 33-824 given i.p. to rats potently inhibit gastrointestinal transit of a charcoal test meal, the doses inhibiting transit by 50% being respectively about 10 and 1 microgram/kg. These intestinal effects are opiate-specific, locally elicited and presumably involve the same action site since they are reversed by the "peripherally selective" narcotic antagonist N-methyl naloxone with apparent pA2 values of 7.34 and 7.10 respectively against morphine and FK 33-824. The calculated pA2 value for naloxone/morphine with the same in vivo test procedure (8.83) and the relative ability of naloxone and N-methyl naloxone to prevent 3H-etorphine binding to rat brain membranes (IC50 43 and 541 nM), indicate different potency ratios between the two narcotic antagonists in the in vitro binding cell-free system (about 1:10) and in vivo (about 1:30), but the latter ratio agrees with published findings in the isolated guinea pig ileum.