Effects of volatile solvents on recombinant N-methyl-D-aspartate receptors expressed in Xenopus oocytes.
1. We have previously shown that toluene dose-dependently inhibits recombinant N-methyl-D-aspartate (NMDA) receptors at micromolar concentrations. This inhibition was rapid, almost complete and reversible. The NR1/2B combination was the most sensitive receptor subtype tested with an IC(50) value for toluene 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-trifluoroethyl ether (flurothyl), on NMDA-induced currents measured in XENOPUS oocytes expressing NR1/2A or NR1/2B receptor 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 NR1/2A subtype. 4. The convulsant solvent flurothyl had no effect on NMDA responses in oocytes but potently inhibited ion flux through recombinant GABA receptors expressed in oocytes. 5. Overall, these results suggest that abused solvents display pharmacological selectivity and that NR1/2B NMDA receptors may be an important target for the actions of these compounds on the brain.
Cruz
S L
SL
Departamento de Farmacología y Toxicología, Cinvestav, IPN, Apartado Postal 22026, 14000 México DF, México.
Balster
R L
RL
Woodward
J J
JJ
D000818:Animals; D001554:Benzene / Q000494:pharmacology; D001555:Benzene Derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D005481:Flurothyl / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects* / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins / Q000187:drug effects; D012997:Solvents / Q000494:pharmacology*; D014240:Trichloroethanes / Q000494:pharmacology; D014835:Volatilization; D014981:Xenopus; D014992:Xylenes / Q000494:pharmacology
D001555:Benzene Derivatives; D018690:Excitatory Amino Acid Agonists; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D012997:Solvents; D014240:Trichloroethanes; D014992:Xylenes; C024268:n-propylbenzene; D016202:N-Methylaspartate; D005481:Flurothyl; D001554:Benzene; C004912:ethylbenzene; C031285:3-xylene