The effects of amfonelic acid on 5-HT metabolism in rat brain.
The non-amphetamine stimulant amfonelic acid (AFA), an inhibitor of dopamine (DA) uptake, has been found to increase the levels of tryptophan (TRYP) and 5-hydroxyindoleacetic acid (5-HIAA) in the rat c. striatum, cerebral cortex, and brain stem. Pretreatment with the DA antagonist haloperidol did not affect this action of AFA in the c. striatum, suggesting that it is independent of the effects of this compound on DA neurons. The duration of action of the effect of AFA on TRYP and 5-HIAA appeared to be longer than that of the increase of the striatal DA metabolites homovanillic acid and 3,4-dihydroxyphenylacetic acid. The increased 5-HIAA concentrations seemed only in part be due to a probenecid-like effect of AFA; evidence for an increased 5-HT synthesis, probably related to the increased TRYP concentrations, was also obtained. This biochemical effect of AFA seems to differ from those reported in the literature on amphetamine and other, related stimulating agents. It might be of interest to see whether corresponding behavioural differences between AFA and these agents can be found.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D006916:5-Hydroxytryptophan / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001933:Brain Stem / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D009268:Nalidixic Acid / Q000031:analogs & derivatives; D009287:Naphthyridines / Q000494:pharmacology*; D010293:Pargyline / Q000494:pharmacology; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism
D009287:Naphthyridines; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D009268:Nalidixic Acid; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan; D010293:Pargyline; D006916:5-Hydroxytryptophan; D011339:Probenecid; C006486:amfonelic acid; D006719:Homovanillic Acid