Stereoselective effects of central alpha 2-adrenergic agonist medetomidine on in vivo catechol activity in the rat rostral ventrolateral medulla (RVLM).
The stereoselective central effects of a novel, highly potent and selective alpha 2-agonist medetomidine on adrenergic neuronal activity, reflected by changes in catechol oxidation current, in the rostral ventrolateral medulla of the halothane-anesthetized rat were examined using in vivo differential normal pulse voltammetry. Dexmedetomidine, the active isomer, significantly decreased catechol oxidation current to 33.4 +/- 4.5% of baseline when given centrally (1 microgram, i.c.v.) and to 10.3 +/- 3.9% of baseline when given systemically (50 micrograms/kg, i.v.). Dexmedetomidine also significantly reduced mean arterial blood pressure by 19.9% following central administration but significantly increased mean arterial blood pressure by 59.9% following systemic administration. Levomedetomidine, the inactive isomer, had no effect on catechol oxidation current or blood pressure. The depressant effects of dexmedetomidine on catechol oxidation current were reversed by the selective alpha 2-adrenoceptor antagonist atipamezole (2 micrograms, i.c.v. or 200 micrograms/kg, i.v.). The results of the present study demonstrate, to our knowledge, for the first time the central stereoselective effects of medetomidine and antagonism by atipamezole on rostral ventrolateral medulla activity in the anesthetized rat.
Hong
M
M
Department of Pharmacology and Toxicology, Faculty of Medicine, Queen's University, Kingston, Ontario, Canada.
Milne
B
B
Loomis
C
C
Jhamandas
K
K
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects*; D002396:Catechols / Q000378:metabolism*; D004594:Electrophysiology; D007093:Imidazoles / Q000494:pharmacology*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D020926:Medetomidine; D008526:Medulla Oblongata / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
D000316:Adrenergic alpha-Agonists; D002396:Catechols; D007093:Imidazoles; D010293:Pargyline; D020926:Medetomidine