Effects of volatile solvents on recombinant N-methyl-D-aspartate receptorsexpressed in Xenopus oocytes

1 We have previously shown that toluene dose-dependently inhibits recombina nt N-methyl-D-aspartate (NMDA) receptors at micromolar concentrations. This inhibition was rapid, almost complete and reversible. The NR1/2B combinati on was the most sensitive receptor subtype tested with an IC50 value for to luene of 0.17 mM. 2 We now report on the effects of other commonly abused solvents (benzene, m-xylene, ethylbenzene, propylbenzene. 1,1,1-trichlorethane (TCE) and those of a convulsive solvent, 2,2,2-trifluororthyl ether (flurothyl), on NMDA-i nduced currents measured in Xenopus oocytes expressing NR1/2A or NR1/2B rec eptor subtypes. 3 All of the alkylbenzenes and TCE produced a reversible inhibition of NMDA -induced currents that was dose- and subunit-dependent, The NR1/2B receptor subtype was several times more sensitive to these compounds than the NR1/2 A subtype. 4 The convulsant solvent flurothyl had no effect on NMDA responses in oocyt es but potently inhibited ion flux through recombinant GABA receptors expre ssed in oocytes. 5 Overall, these results suggest that abused solvents display pharmacologic al selectivity and that NR1/2B NMDA receptors may be an important target fo r the actions of these compounds on the brain.