CALCIUM ANTAGONIST ACTIVITY OF METHADONE, L-ACETYLMETHADOL AND L-PENTAZOCINE IN RAT AORTIC STRIP

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Abstract
The physiologic evidence that methadone and related compounds can function as Ca antagonists is described. Methadone (1 .times. 10-5 - 1 .times. 10-4 M) inhibited the contraction of the isolated rat aortic strip preparation produced by KCl, norepinephrine, l-pentazocine or morphine. Methadone was most effective in diminishing aortic contractions which were highly dependent on the extracellular Ca concentration. The d- and l-isomers of methadone were equipotent inhibitors of aortic contraction. l-Acetylmethadol (1 .times. 10-6 - 1 .times. 10-5 M) was a potent vascular contraction inhibitor. l-Pentazocine inhibited its own ability to contract the aorta as the dose was raised above 3 .times. 10-5 M. The aortic contraction inhibition produced by methadone, l-acetylmethadol and l-pentazocine was overcome by raising the Ca concentration in the tissue baths. The inhibition of contraction and the apparent Ca antagonist activity of these drugs best correlates with their lipid solubility. Since Ca is a critical regulator of cellular function, the Ca-antagonist action of methadone and l-acetylmethadol may prove important in mediating some of their pharmacologic and toxicologic effects.