4-Methylmethamphetamine (4-MMA), also known as mephedrine, is a putative stimulant and entactogen drug of the amphetamine family. It acts as a serotoninâÂÂnorepinephrineâÂÂdopamine releasing agent (SNDRA). The drug is the ò-deketo analogue of mephedrone (4-methylmethcathinone; 4-MMC) and the N-methyl analogue of 4-methylamphetamine (4-MA).
4-MMA acts as a potent and well-balanced serotoninâÂÂnorepinephrineâÂÂdopamine releasing agent (SNDRA). It induces hyperlocomotion and stereotypy (psychostimulant-like effects) as well as hyperthermia in mice, similarly to methcathinone.
In contrast to methamphetamine and methcathinone, 4-MMA appears to produce minimal dopaminergic neurotoxicity in mice. Conversely, mephedrone shows no dopaminergic neurotoxicity at all in mice. It was theorized that 4-methyl and ò-keto substitutions on amphetamines may result in loss of activity at the vesicular monoamine transporter 2 (VMAT2), loss of elevations of cytosolic dopamine concentrations, and consequent loss of dopaminergic neurotoxic potential. Accordingly, the dopaminergic neurotoxicity of 4-MMA was greatly enhanced by the dopamine precursor levodopa (<small>L</small>-DOPA), the monoamine oxidase inhibitor (MAOI) pargyline, and methamphetamine (a VMAT2 inhibitor/reverser), all of which are known to increase the cytosolic pool of dopamine. However, in contrast to 4-MMA, the dopaminergic neurotoxicity of methcathinone was enhanced only by levodopa and of mephedrone was enhanced only by methamphetamine.