Alpha-2 adrenoreceptors probably do not mediate the immobility produced by inhaled anesthetics.
Agonism of alpha-adrenoreceptors has a powerful anesthetic result mediated, in part, by effects on the spinal cord. Alpha-adrenoreceptor agonists (e.g., dexmedetomidine) can decrease the minimum alveolar anesthetic concentration (MAC) of inhaled anesthetics (e.g., halothane) to zero, with an apparently additive interaction between halothane and dexmedetomidine. We tested whether the capacity of the inhaled anesthetic isoflurane to produce immobility in the face of noxious stimulation resulted from agonism of alpha-adrenoreceptors. MAC (the concentration required to eliminate movement in response to a noxious stimulus in 50% of subjects) of isoflurane was determined before and after intraperitoneal administration of the alpha-adrenoreceptor antagonists yohimbine and atipamezole. The doses of yohimbine and atipamezole equaled or exceeded those that reverse the ability of agonism of alpha-adrenoreceptors to decrease MAC. Smaller doses of yohimbine or atipamezole slightly increased (by 10%) the MAC of isoflurane, an increase we interpret as the result of blockade of a small amount of tonically active alpha-adrenoreceptor activity. Doses five-fold larger did not change MAC. Doses 10-fold larger decreased MAC. We conclude that alpha-adrenoreceptors do not or minimally mediate the capacity of inhaled anesthetics to produce immobility.


CONCLUSIONS
Although stimulation (agonism) of alpha-2 adrenoreceptors can decrease the inhaled anesthetic concentration required to produce immobility in the face of noxious stimulation, blockade of alpha-2 adrenoreceptors minimally affects the concentration. Thus, augmentation of the effect of alpha-2 adrenoreceptors is not an appreciable part of the mechanism whereby inhaled anesthetics produce immobility.
Eger
Edmond I
EI
Department of Anesthesia and Perioperative Care, University of California, San Francisco.
Xing
Yilei
Y
Laster
Michael J
MJ
Sonner
James M
JM
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology; D008297:Male; D009068:Movement / Q000187:drug effects; D010146:Pain / Q000523:psychology; D010812:Physical Stimulation; D011650:Pulmonary Alveoli / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D018685:Anesthetics, Inhalation; D007093:Imidazoles; D018341:Receptors, Adrenergic, alpha-2; C050701:atipamezole; D015016:Yohimbine; D007530:Isoflurane