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.