New psychoactive substances (NPS) are typically synthesized in clandestine laboratories in an attempt to chemically modify already federally regulated drugs in an effort to circumvent the law. Drugs derived from a phenethylamine pharmacophore, such as 4-chloroamphetamine and 3,4-methylenedioxymethamphetamine (MDMA), reliably induce thermogenesis and serotonergic deficits in the striatum and hippocampus of rodents. 4-methylamphetamine (4-MA), a relative newcomer to the NPS scene, was originally investigated in the mid-1900 s as a potential anorexigenic agent. With its phenethylamine pharmacophore, 4-MA was hypothesized to produce similar toxicological alterations as its chemical analogs. In the present study, three doses (1.0, 2.5, and 5.0 mg/kg, ip.) of 4-MA were administered to rats twice daily for two days. Core temperature data were calculated and analyzed as temperature area under the curve (TAUC). On the second day of dosing, a hypothermic response to 4-MA (2.5 and 5.0 mg/kg) was noted between 0.5 and 2.0 h post-treatment. Only the highest dose of 4-MA decreased body weight on the second day of treatment and maintained this reduction in weight for seven days after treatment ceased. None of the doses of 4-MA evaluated significantly altered serotonin levels in the hippocampus or striatum seven days after final treatment. The present findings demonstrate that the 4-methyl substitution to amphetamine generates a pharmacological and toxicological profile that differs from other similar phenethylamine analogs.
Keywords: 4-methylamphetamine; Designer drug; Hippocampus; Serotonin; Striatum; Thermogenesis.
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