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Anesth Analg 1988; 67:611-615
© 1988 International Anesthesia Research Society
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Anesthetic and Hemodynamic Effects of the Stereoisomers of Medetomidine, an {alpha}2-Adrenergic Agonist, in Halothane-Anesthetized Dogs

Ross G. Vickery, BS, Brett C. Sheridan, Ira S. Segal, MD, and Mervyn Maze, MB

Received from the Anesthesiology Service (112A), Veterans Administration Medical Center, Palo Alto, California, and the Department of Anesthesia, Stanford University, Stanford, California.

Abstract

The anesthetic-sparing and hemodynamic effects of the Stereoisomers of the highly selective {alpha}2-adrenergic agonist medetomidine were studied in halothane-anesthetized dogs. Male beagles were anesthetized with halothane in oxygen. After a 2-hour equilibration period, halothane MAC and baseline hemodynamic 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 {alpha}2-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.

Key Words: SYMPATHETIC NERVOUS SYSTEM, PHARMACOLOGY—medetomidine • POTENCY, ANESTHETIC—MAC




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 1988 by the International Anesthesia Research Society.