Search

In earlier studies (Ivanov, Staneva-Stoycheva, 1984) we have found an inhibitory effect of metamyzole (Analgin-Pharmachim) on the contractile responses of electrically stimulated guinea-pig ileum and mouse vas deferens, which is antagonized by naloxone. In the present study an attempt is made to clarify whether these presynaptic effects of metamyzole are due to direct interaction with presynaptic opiate receptors. The method of radioligand binding of /3H/-naloxone to the opiate receptors in a crude membrane fraction of rat brain was used. It was found that in the wide concentration range used (10(-5)-10(-9) M), metamyzole does not compete with /3H/-naloxone for binding to the receptor sites. The biochemical study has shown that the presynaptic opiate receptors do not participate in the mechanism of the presynaptic effects of metamyzole, established in earlier studies.

The effect of Analgine in different concentrations on the contractions of electrically stimulated isolated guinea-pig ileum and mouse vas deferens is studied and compared with the effect of morphine on the same isolated organs. Analgine causes morphine-like but weaker concentration-dependent inhibitory effect (IC50 = 5.75 X 10(-6) M) on guinea-pig ileum, which is completely eliminated by naloxon and 4-aminopyridine. Upon simultaneous administration of morphine analgine, potentiation of the effect of morphine is observed, which is also eliminated by naloxon and 4-aminopyridine. Analgine has a weaker inhibitory effect (IC50 = 1 X 10(-4) M) on the contractions of mouse vas deferens, compared with its effect on the ileum. The same is also valid for the independent and combined with analgine effect of morphine, completely eliminated only by 4-aminopyridine, but not by naloxon. In cases of reduced Na+-concentration in the medium, the effect of analgine on the contractions of the ileum is weaker (IC25 = 4.43 X 10(-5) M), while that of morphine is stronger compared with normal conditions. Increased Ca++-concentration is parallelled by a weaker effect of analgine (IC25 = 4.76 X 10(-5) M), unlike the effect of morphine which is potentiated. It is possible to assume some interaction of analgine with a definite type of presynaptic opiate receptors, similar or identical to these receptors which are responsible for the peripheral effects of the narcotic analgesics.