The effects of aminorex and related compounds on brain monoamines and metabolites in CBA mice.
Acute and long-term neurochemical effects of aminorex, an appetite-suppressing drug related to amphetamine in chemical structure, and stereoisomers of its analogues were examined and compared with those of 3.4-methylenedioxymethylamphetamine (MDMA) and fenfluramine. Aminorex and its analogues, with exception of 4S, 5S-dimethylaminorex, did not cause the long-term neurotransmitter depletion in either the dopaminergic or 5-HT-ergic systems that was observed after MDMA or fenfluramine in CBA mice. These results are discussed in terms of possible structurally related mechanisms of neurotoxicity. The acute neurochemical effects showed that aminorex and analogues all produced increases in 5-hydroxytryptamine (5-HT) levels, unlike fenfluramine and MDMA in the present study or in published data. This suggests that inhibition of 5-HT metabolism, rather than direct 5-HT release, may be involved in their anorectic effect. The parallel study of acute dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) changes suggest that in CBA mice MDMA may be a better dopamine releaser and this may contribute to its dopaminergic neurotoxicity. However the ability to release dopamine or 5-HT, or both, may be important, but not the only factor involved in causing the long-term neurotoxicity observed with amphetamine derivatives.
Zheng
Y
Y
Department of Pharmacology, University of Otago, Dunedin, New Zealand. yiwen.zheng@stonebow.otago.ac.nz
Russell
B
B
Schmierer
D
D
Laverty
R
R
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000635:Aminorex / Q000633:toxicity*; D000818:Animals; D001067:Appetite Depressants / Q000633:toxicity*; D015306:Biogenic Monoamines / Q000032:analysis* / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D004298:Dopamine / Q000032:analysis; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology; D012701:Serotonin / Q000032:analysis
D001067:Appetite Depressants; D015306:Biogenic Monoamines; D015102:3,4-Dihydroxyphenylacetic Acid; D000635:Aminorex; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine