Neurochemical effects of an acute treatment with 4-methylaminorex: a new stimulant of abuse.
4-Methylaminorex (4-MAX) is an amphetamine analog which has recently gained attention due to its potential as a stimulant of abuse. The present study characterized the acute neurochemical changes elicited after a single dose of 4-MAX. Thus, dose-response and time-response studies were conducted in order to assess the effects of this drug on monoaminergic and neuropeptide systems in extrapyramidal and limbic structures. The most dramatic responses in the dose-effect experiments (animals killed 3 h after treatment) were a 2-fold increase in neostriatal homovanillic acid levels and a decrease in neostriatal tryptophan hydroxylase activity to 33% of control in the 20 mg/kg group. Because all animals in the 20 mg/kg group experienced convulsions, 10 mg/kg was used for the time-response studies. The most striking effects in these studies included a reduction in dopamine concentrations to 71% of control, and an increase to 270% of control in the concentrations of dihydroxyphenylacetic acid 30 min after 4-MAX administration. In addition, neostriatal neurotensin and dynorphin A levels increased to approximately 200 and 400% of control, respectively, 18 h after a 10 mg/kg dose. These data suggest that 4-MAX is a potent dopamine releaser, which decreases tryptophan hydroxylase activity in a manner similar to other amphetamine-related drugs. However, in contrast to other amphetamine analogs, 4-MAX has potent convulsant actions.
Bunker
C F
CF
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112.
Johnson
M
M
Gibb
J W
JW
Bush
L G
LG
Hanson
G R
GR
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003292:Convulsants; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D013287:Illicit Drugs / Q000494:pharmacology*; D008297:Male; D009479:Neuropeptides / Q000378:metabolism; D010080:Oxazoles / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014365:Tryptophan Hydroxylase / Q000378:metabolism
D015306:Biogenic Monoamines; D000697:Central Nervous System Stimulants; D003292:Convulsants; D013287:Illicit Drugs; D009479:Neuropeptides; D010080:Oxazoles; C000081:4-methylaminorex; D014365:Tryptophan Hydroxylase; D006719:Homovanillic Acid