Actions of the hypnotic anaesthetic, dexmedetomidine, on noradrenaline release and cell firing in rat locus coeruleus slices.
We have examined the effects of the highly selective alpha 2-adrenoceptor agonist, dexmedetomidine, on noradrenaline release and cell firing in isolated, superfused slices of rat locus coeruleus. Dexmedetomidine decreased both noradrenaline release and cell firing rate in a concentration-dependent fashion, with an EC50 of 3.97 (SEM 0.97) x 10(-9) mol litre-1 for noradrenaline release and 0.92 (0.53) x 10(-9) mol litre-1 for unit activity. Both effects were reversed completely by the selective alpha 2 antagonist, atipamezole 10(-6) mol litre-1. These results suggest that cell firing and noradrenaline release are under alpha 2 receptor control and that dexmedetomidine potently stimulates these receptors. We conclude that these effects are consistent with the locus coeruleus being a major site of action of the hypnotic anaesthetic alpha 2 agonists.
Jorm
C M
CM
Anaesthetics Unit, London Hospital Medical College, Royal London Hospital, Whitechapel.
Stamford
J A
JA
D000200:Action Potentials / Q000187:drug effects; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008125:Locus Coeruleus / Q000502:physiology*; D020926:Medetomidine; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; C050701:atipamezole; D020926:Medetomidine; D009638:Norepinephrine