Anesthetic and Hemodynamic Effects of the Stereoisomers of Medetomidine, an ??2-Adrenergic Agonist, in Halothane-Anesthetized Dogs

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Abstract
Dynamic functions were determined. DL-(n = 7), D-(n = 5), or L-medetomidine (n = 5) at 1, 3, and 10 μg/kg was administered via a right atrial port over 15 minutes while each dog was given halothane at the MAC dose for that animal. Twenty minutes after the end of infusion (when the hemodynamic variables were stable), hemodynamic function was reassessed. Halothane MAC was then redetermined. MAC for halothane significantly decreased after DL-medetomidine administration in a dose-dependent fashion to the extent that at the highest dose (10 μg/kg) the halothane MAC was <0.1%. This effect could be mimicked by the D-isomer, whereas the L-isomer was without effect. Neither isomer changed the mean arterial pressure, whereas only the D-isomer significantly decreased heart rate and cardiac output. Medetomidine, the highly selective α2-adrenergic agonist, reduces the MAC for volatile anesthesia by a greater degree than with any other physiologic, pharmacologic, or pathologic intervention thus far reported. The fact that this effect is stereospecific suggests a structure activity relation that can be accounted for by a homogeneous receptor population. The role of medetomidine as a supplemental anesthetic agent appears promising and requires further investigation. Supported in part by the Veterans Administration, the American Heart Association, California Affiliate No. 86-N133 and N.I.H. GM 30232. Dr. Maze is a recipient of the B.B. Sankey Award. Address correspondence to Mr. Maze, Anesthesiology Service (112A), 3801 Miranda Avenue, Palo Alto, CA 94304. We gratefully acknowledge the information and compounds provided by Drs. Risto Lammintausta (medetomidine) and Alan Roach (idazoxan). Accepted for publication February 3, 1988. © 1988 International Anesthesia Research Society...