Pharmacological effects of meptazinol and its enantiomers on guinea-pig ileum and mouse vas deferens.

Electrically induced twitch responses of mouse vas deferens and guinea-pig ileum were inhibited by morphine, normorphine and the peptide opioid agonist RX783006; naloxone blocked the effects of all three opioid agonists yielding Ke values which were not significantly different and which were within the range (1-4 nM) expected for mu-type receptors. At concentrations between 0.1 and 10 microM (+)-meptazinol inhibited the twitch response of the ileum while (-)-meptazinol produced potentiation. Naloxone (20 nM) completely blocked the effect of (+)-meptazinol and further increased the potentiation produced by (-)-meptazinol. In the mouse vas deferens preparation neither isomer affected the electrically induced twitch response at concentrations below 5 microM and higher concentrations (10-300 microM) produced potentiation. Naloxone (20 nM) did not modify this effect. It is concluded that both isomers are opioid agonists on the mu-receptors in guinea-pig ileum but not in mouse vas deferens and that a cholinergic component, which may contribute to the action of meptazinol in-vivo, is present to a smaller extent in the (+)-isomer.