Dexmedetomidine decreases halothane anesthetic requirements in rats

alpha 2-Adrenergic agonists, such as clonidine, reduce the dose requirements for halothane. Medetomidine is more selective as a full agonist for central alpha 2-adrenoceptors than clonidine and is available as both an active (d) and an inactive (l) isomer. We have used the d-isomer to probe the mediating mechanism for the MAC-sparing effect of this alpha 2-agonist in rats. The dose of halothane which rendered 50% of animals insensitive to a painful stimulus (halothane MAC) was determined in rats (150-200 g) before and after d- or l-medetomidine, 10, 30 and 100 micrograms/kg or saline i.p. To determine whether alpha 2-adrenoreceptors mediated the MAC-sparing effect of dexmedetomidine (d-medetomidine), cohorts of rats (n = 6 for each dose) were pretreated with idazoxan, 10 mg/kg i.p., the highly selective alpha 2-antagonist. To determine whether dexmedetomidine's MAC-reducing action was mediated in part through either opiate or adenosine receptors, groups of rats were pretreated with either naltrexone, 5 mg/kg i.p., an opiate antagonist; or 8-phenyltheophylline (8-PT), 2.5 mg/kg i.p., an A1 adenosine antagonist. To determine whether postsynaptic mechanisms mediate the anesthetic-sparing effect of dexmedetomidine, rats were depleted of central norepinephrine stores with 6-OHDA and 4 days later MAC was determined before and after each dose of dexmedetomidine. Dexmedetomidine dose-dependently decreased MAC for halothane such that at the highest dose, halothane could be discontinued for up to 30 min without eliciting a response to tail-clamping. Idazoxan completely prevented the MAC-reducing action of dexmedetomidine, while naltrexone and 8-PT were without effect.(ABSTRACT TRUNCATED AT 250 WORDS)