An antinociceptive profile of kojic amine: an analogue of gamma-aminobutyric acid (GABA).
Kojic amine [2-(aminomethyl)-5-hydroxy-4H-pyran-4-one], an analogue of gamma-aminobutyric acid (GABA), produced dose-related, but short-lived, antinociceptive activity in the 48 degrees C [ED50 = 9.2 (8.2-10.3) mg/kg i.p.] and 55 degrees C [ED50 = 13.8 (12.2-15.7) mg/kg i.p.] hot-plate tests in the mouse. The antinociceptive activity of kojic amine at 48 degrees C was found to be insensitive to bicuculline (1.0 mg/kg i.p.) and picrotoxin (0.5 mg/kg i.p.). At this temperature, antinociception was distinctly separate from the impairment of motor function (measured by a rotorod assay) and was not significantly affected by prior treatment with the cholinergic antagonist, atropine sulfate (10.0 mg/kg i.p.). However, at 55 degrees C, the antinociceptive effect of a large dose (20 mg/kg i.p.) of kojic amine was significantly attenuated by similar pretreatment with atropine sulfate, but not by the peripheral cholinergic antagonist, atropine methylnitrate (10.0 mg/kg i.p.). Kojic amine exhibited no significant interaction with haloperidol (0.5 mg/kg i.p.) at this temperature. In animals made tolerant to morphine, THIP or baclofen, there was analgesic cross-tolerance between kojic amine, morphine and baclofen but not between kojic amine and THIP. It is suggested that kojic amine-induced antinociception is similar to that produced by both THIP and baclofen. Thus, kojic amine represents a unique tool with which to study GABA-ergic antinociceptive processes.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001286:Atropine Derivatives / Q000494:pharmacology; D001418:Baclofen / Q000494:pharmacology; D007555:Isoxazoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D010146:Pain / Q000503:physiopathology*; D011714:Pyrans / Q000494:pharmacology*; D011753:Pyrones / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives*
D001286:Atropine Derivatives; D007555:Isoxazoles; D011714:Pyrans; D011753:Pyrones; D005680:gamma-Aminobutyric Acid; C018990:kojic amine; D009020:Morphine; D001285:Atropine; C006649:methylatropine; D001418:Baclofen; C015542:gaboxadol