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To demonstrate the difference in the action mechanisms of morphine (Mor), pentobarbital (Pent) and ethanol (EtOH), comparative studies on the inhibitory effect on the electrical stimulation (ES)-evoked contractions of isolated mouse vas deferens (MVD) were undertaken. All the drugs inhibited the ES-evoked contractions of MVD preparations in a concentration-dependent manner, however, the effects were completely different among 3 drugs in the preparations after incubation in the medium containing each drug and also after acute or chronic treatment with the drugs. The differences among 3 drugs are as follows: 1) The in vitro incubation with Mor, but not with Pent and EtOH developed tolerance. 2) MVD from Mor and EtOH tolerant animals were also tolerant to the inhibitory effect of Mor and EtOH in vitro, respectively. 3) K+ and Ca2+ stimulated the contractions of MVD and the effect was enhanced further after incubation in Mor. 4) The administration of Mor and Pent dose-dependently enhanced the effect of K+ and Ca2+, but this effect of Mor was lost following repeated injections. 5) No cross tolerance was developed among 3 drugs in the inhibitor effect following in vitro incubation or in vivo treatment. Thus, the effects of in vitro incubation with Mor, Pent and EtOH, and acute or chronic administration of the drugs on the response of isolated MVD preparations are different from each other suggesting the difference in the underlying mechanisms of the drugs.

journal of pharmacobio-dynamics

Comparative studies on the inhibitory effect of morphine, pentobarbital and ethanol on the electrically evoked contractions of isolated mouse vas deferens.