Spinal antinociception by dexmedetomidine, a highly selective alpha 2-adrenergic agonist.
The antinociceptive effects of dexmedetomidine, a highly selective new alpha 2-adrenoceptor agonist, were evaluated in rats after intrathecal, intraperitoneal and subcutaneous administration. Antinociception was tested using the tail-flick method. Both 3 and 6 micrograms of intrathecal dexmedetomidine produced maximal antinociception within 10 min. The effect lasted for up to 6 hr. The smaller dose of 1.5 micrograms produced a mean antinociception of 50% (of the maximum possible effect, MPE%) which lasted for about 2 hr. Subcutaneous atipamezole, a specific alpha 2-adrenergic antagonist completely abolished the antinociception produced by intrathecal dexmedetomidine. When given intraperitoneally, dexmedetomidine produced on average a 50% antinociceptive effect with the highest dose of 60 micrograms/kg. The lower doses of 10 and 30 micrograms/kg were ineffective. After subcutaneous administration a maximal effect was achieved with 120 micrograms/kg, a 70% effect, on average, with 60 micrograms/kg and a short lasting effect of 60% with 30 micrograms/kg. In conclusion, dexmedetomidine is a very potent antinociceptive agent when given intrathecally to rats.
Department of Anaesthesia, University of Helsinki, Finland.
E A
EA
Kalso
R
R
Pöyhiä
P H
PH
Rosenberg
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000700:Analgesics; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D008297:Male; D020926:Medetomidine; D010147:Pain Measurement; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000700:Analgesics; D007093:Imidazoles; C050701:atipamezole; D020926:Medetomidine