Studies on the interaction between ethanol and amfonelic acid.
Amfonelic acid (AFA), a non-amphetamine central stimulant dose-dependently reduced the hypnotic effect of ethanol in C57B1/6 mice. It did not enhance the elimination of ethanol. Amfonelic acid failed to modify the duration of pentobarbitone-induced hypnosis or the ethanol-induced hypothermia in these animals. Combined treatment with amfonelic acid and a lipophilic alpha 1-adrenoceptor agonist was not more effective than amfonelic acid alone in blocking ethanol hypnosis. The stimulation of locomotor activity by amfonelic acid in C57B1/6 mice was more sensitive to the blocking effect of ethanol than stimulation induced by d-amphetamine. The blocking effect of amfonelic acid, but not that of d-amphetamine, on the effects of ethanol developed tolerance. In pimozide-pretreated mice, amfonelic acid failed to reduce the ethanol-induced hypnosis. Hence it appears that dopamine (DA) released by amfonelic acid is responsible for its antagonism of ethanol. However, though amfonelic acid acted as a strong releaser of DA in Swiss-Webster, CD-1, DBA-2 and BALB/c mice, in these strains it failed to reduce the effect of ethanol. Moreover, methylphenidate, a dopaminergic stimulant, which acts by a mechanism similar to that of amfonelic acid was not effective in reducing the hypnotic effect of ethanol in C57B1/6 mice. For these reasons, additional mechanisms may have to be considered to explain this strain-dependent effect of amfonelic acid.
D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009268:Nalidixic Acid / Q000031:analogs & derivatives; D009287:Naphthyridines / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects*; D013045:Species Specificity
D009287:Naphthyridines; D009268:Nalidixic Acid; D000431:Ethanol; C006486:amfonelic acid