Differences in Efficacies Between Morphine and Methadone Demonstrated in the Guinea Pig Ileum: A Possible Explanation for Previous Observations on Incomplete Opioid Cross-Tolerance.

Autor: Ivarsson, Mikael, Neil, Anders
Zdroj: Pharmacology & Toxicology; 1989, Vol. 65 Issue 5, p368-371, 4p
Abstrakt: We have compared the effectiveness of morphine and methadone as agonists in untreated guinea-pig longitudinal muscle preparations and after their treatment with the specific opioid receptor alkylating agent β-chloronaltrexamine. In untreated ilea, the naloxone pA2 was 8.5 to both morphine and methadone, and their dose-response curves were parallel. After alkylation, the dose-response curve for morphine was shifted to the right with a decreased maximal effect. It was found that about 70% of the receptors were inactivated by the treatment, corresponding to a morphine receptor occupancy at IC50 of about 24%. The maximal effect of methadone was not decreased by the same β-chloronaltrexamine treatment, indicating a much higher efficacy or receptor reserve for the drug. The possibility that differences in efficacies could account for previously reported heterogeneities in actions of opioids, such as assymmetries in cross-tolerance towards morphine and methadone in experimental animal and man, is discussed. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index