The alpha 2-adrenoceptor agonist dexmedetomidine increases the apparent potency of the volatile anesthetic isoflurane in rats in vivo and in hippocampal slice in vitro.
Alpha 2-adrenoceptor agonists such as clonidine are sedatives and enhance the effectiveness of several different kinds of anesthetics. This study was performed to quantitate the effect of dexmedetomidine, a novel alpha 2-adrenoceptor agonist, on the action of the volatile anesthetic agent isoflurane in rats in vivo. A separate set of experiments in rat hippocampal slices was designed to determine whether isoflurane and dexmedetomidine exerted similar effects on synaptic transmission in vitro and to examine the interaction between the two agents. In vivo, dexmedetomidine (100 micrograms/kg i.p.) reduced isoflurane minimum alveolar anesthetic requirement (MAC), determined by loss of response to tail pinch, by approximately 90%. In hippocampal CA1 neurons, on the other hand, there was a relatively small potentiation of the effects of isoflurane at the maximally effective dexmedetomidine concentration (1 nM). The hippocampal CA1 area, at least in the slice preparation, may thus not be representative of the CNS site(s) at which alpha 2 adrenoceptor agonists lessen anesthetic requirement in vivo.
Department of Anesthesia, Stanford University School of Medicine, CA 94305-5123.
M K
MK
Savola
M B
MB
MacIver
V A
VA
Doze
J J
JJ
Kendig
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Maze
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D004357:Drug Synergism; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D020926:Medetomidine; D051381:Rats; D011919:Rats, Inbred Strains
D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D007530:Isoflurane; D020926:Medetomidine