Further characterization of the receptor mechanism involved in the antidysrhythmic effect of dexmedetomidine on halothane/epinephrine dysrhythmias in dogs.
BACKGROUND
alpha 2 Adrenoceptors in the central nervous system mediate various physiologic processes, including cardiovascular control. Recently, some of these actions have been reported to be mediated by a nonadrenergic receptor, namely an imidazoline receptor. The authors previously reported that dexmedetomidine, a selective alpha 2 agonist, prevents the genesis of halothane-epinephrine dysrhythmias through a central mechanism. Because dexmedetomidine also binds to imidazoline receptors, we performed the current study to examine the precise receptor mechanism involved in the antidysrhythmic property of dexmedetomidine.


METHODS
Adult mongrel dogs were anesthetized with halothane (1.3%) and monitored continuously for systemic arterial pressure and premature ventricular contractions. The dysrhythmogenic dose of epinephrine was defined as the smallest dose producing four or more premature ventricular contractions within 15-s period. We examined the antidysrhythmic action of dexmedetomidine in the presence of two kinds of alpha 2 antagonists, that is, agents that label imidazoline receptors and exert a pharmacologic action through imidazoline receptors (idazoxan and atipamezole) and agents that are nonimidazoline compounds and are lacking in pharmacologic action through imidazoline receptors (rauwolscine and L-659,066). They were given cerebroventricularly.


RESULTS
Idazoxan and atipamezole significantly inhibited the antidysrhythmic action of dexmedetomidine, whereas rauwolscine and L-659,066 did not.


CONCLUSIONS
Because alpha 2 antagonists having imidazoline or imidazole structures inhibited the antidysrhythmic action of dexmedetomidine, and the inhibition produced by the non-imidazoline alpha 2 antagonists was not significant, imidazoline receptors in the central nervous system are more responsible for the antidysrhythmic action of dexmedetomidine than are alpha 2 adrenoceptors.
D000316:Adrenergic alpha-Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004146:Dioxanes / Q000494:pharmacology; D004285:Dogs; D004347:Drug Interactions; D004837:Epinephrine / Q000009:adverse effects*; D005260:Female; D006221:Halothane / Q000009:adverse effects*; D006439:Hemodynamics / Q000187:drug effects; D019329:Idazoxan; D007093:Imidazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D054755:Imidazoline Receptors; D008297:Male; D020926:Medetomidine; D011955:Receptors, Drug / Q000187:drug effects*; D018879:Ventricular Premature Complexes / Q000139:chemically induced* / Q000188:drug therapy*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D007093:Imidazoles; D054755:Imidazoline Receptors; D011955:Receptors, Drug; C050701:atipamezole; D020926:Medetomidine; D006221:Halothane; D019329:Idazoxan; D004837:Epinephrine