Calcium antagonist activity of methadone, l-acetylmethadol and l-pentazocine in the rat aortic strip.
These studies described physiologic evidence that methadone and related compounds can function as calcium antagonists. Methadone (1 X 10(-5)-1 X 10(-4) M) inhibited the contraction of the isolated rat aortic strip preparation produced by potassium chloride, norepinephrine, l-pentazocine or morphine. Methadone was most effective in diminishing aortic contractions which were highly dependent on the concentration of extracellular calcium. The d- and l-isomers of methadone were equipotent inhibitors of aortic contraction. l-Acetylmethadol (1 X 10(-6)-1 X 10(-5) M) was a potent inhibitor of vascular contraction. l-Pentazocine inhibited its own ability to contract the aorta as the dose was raised 3 X 10(-5) M. The inhibition of aortic contraction produced by methadone, l-acetylmethadol and l-pentazocine was overcome by raising the concentration of calcium in the tissue baths. The inhibition of contraction and the apparent calcium-antagonist activity of these drugs best correlates with their lipid solubility. Since calcium is a critical regulator of cellular function, the calcium-antagonist action of methadone and l-acetylmethadol may prove to be important in mediating some of their pharmacologic and toxicologic effects.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002118:Calcium / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004347:Drug Interactions; D066298:In Vitro Techniques; D008297:Male; D008691:Methadone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008692:Methadyl Acetate / Q000494:pharmacology*; D009020:Morphine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010423:Pentazocine / Q000494:pharmacology*; D051381:Rats; D013237:Stereoisomerism
D009020:Morphine; D008692:Methadyl Acetate; D010423:Pentazocine; D002118:Calcium; D008691:Methadone