Separate noradrenergic receptors could mediate clonidine-induced antinociception.
The antinociceptive effect of clonidine on a response to painful stimulation mediated by supraspinal structures was recorded after s.c. administration of the drug in doses from 50 up to 2000 micrograms/kg. Both low and high doses of clonidine produced antinociception on the pain threshold studied. A careful analysis of the dose-response curve showed, however, that the net effect recorded involved the sum of responses from at least two functional systems or receptor sites. When the dose-response relationship of clonidine-induced antinociception was studied after alpha-1 receptor blockade by means of phenoxybenzamine, it was found that this effect comprised contributions from different neurotransmitter systems. These results are discussed in terms of the possibility that separate adrenergic receptors mediate clonidine antinociception at different levels in the pain transmission. The determinant of the population of receptors being activated after systemic administration of clonidine is the dose given.
D000700:Analgesics; D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D010643:Phenoxybenzamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*; D014828:Vocalization, Animal / Q000187:drug effects
D000700:Analgesics; D011941:Receptors, Adrenergic; D010643:Phenoxybenzamine; D003000:Clonidine