Pharmacological characterization of BNMPA (alpha-benzyl-N-methylphenethylamine), an impurity of illicit methamphetamine synthesis

alpha-Benzyl-N-methylphenethylamine (BNMPA), an impurity of illicit methamphetamine synthesis, has previously been reported to produce convulsions in mice without affecting spontaneous locomotor activity or altering methamphetamine-induced increases in spontaneous activity. In this study the in vitro effects of BNMPA on a variety of neuronal receptor types was determined to better characterize the pharmacological actions of this novel compound. BNMPA and N-demethyl-BNMPA fully displaced the dopamine transporter selective ligand [H-3]CFT (2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane) from rat striatal membranes with K-i values (mean +/- S.E.M) of 6.05 mu M +/- 0.15 and 8.73 mu M +/- 1.66, respectively. BNMPA also inhibited [H-3]dopamine uptake into striatal synaptosomes with an IC50 value of 5.1 +/- 1.4 mu M. The basal efflux of [H-3]dopamine from striatal slices was slightly enhanced by BNMPA only at concentrations greater than or equal to 100 mu M. BNMPA had no effect on [H-3]norepinephrine efflux from hippocampal slices. BNMPA displaced tritiated paroxetine and prazosin binding from rat cortical membranes with K-i values of 14.5 mu M and 11.7 mu M respectively. In electrophysiological studies, BNMPA (100 mu M) had no significant effects on either GABA(A) Cl- currents in cultured neurons or non-NMDA glutamate receptors expressed in oocytes. However, BNMPA significantly inhibited NMDA-stimulated currents in oocytes expressing the NR1/2A or NR1/2C receptor subunit combinations (IC50 values = 24.6 +/- 1.8 and 24.0 +/- 1.5 mu M, respectively). This inhibition was rapid, reversible and voltage-dependent. These results indicate that BNMPA has multiple sites of action in the CNS that could be important in modulating a variety of behavioral effects upon exposure to this synthetic byproduct of illicit methamphetamine synthesis.