title: Effects of inhaled toluene and 1,1,1-trichloroethane on seizures and death produced by N-methyl-D-aspartic acid in mice.
abstract: Evidence exists that some abused solvents have N-methyl-D-aspartic acid (NMDA) antagonist activity, although which of their effects may be related to this mechanism is not well understood. The effects of toluene and 1,1,1-trichloroethane (TCE) on NMDA-induced seizures in mice were studied using three experimental protocols: (a) animals injected i.p. with 120 or 170 mg/kg NMDA and immediately afterwards exposed to solvent vapors or air for 30 min (co-exposure protocol); (b) mice exposed for 30 min to solvent or air, then injected with NMDA and placed in the chamber for a second 30-min exposure (pre-exposure+co-exposure protocol); and (c) mice that inhaled 4000 ppm toluene or air for 30 min twice a day, 6 h apart, for 7 days, and were injected with 120 mg/kg NMDA immediately before a 30-min toluene exposure (repeated exposure protocol). When given acutely, toluene, but not TCE, produced concentration-dependent protection against NMDA-induced seizures. Higher concentrations of toluene were also effective against the lethal effects produced by 170 mg/kg NMDA. Clearer effects were seen when the pre-exposure+co-exposure protocol was followed. Under these conditions the IC(50) for toluene was 739 ppm (653-825) against seizure occurrence and 2127 ppm (1966-2288) against lethality. Repeated exposure to toluene did not result in tolerance to its anticonvulsant effects. These results are consistent with the in vitro effects described for toluene as a noncompetitive NMDA antagonist and as a compound that enhances GABAergic transmission. The lack of protective effects of TCE is not consistent with its in vitro actions.
authors.affiliation: Departamento de Farmacobiología, Cinvestav, IPN. Calzada de los Tenorios #235, Col. Granjas Coapa, 14330 Mexico, D.F., Mexico. cruz_farma@yahoo.com
authors.forename: Silvia Lorenia
authors.initials: SL
authors.lastname: Cruz
authors.forename: Marcia Yvette
authors.initials: MY
authors.lastname: Gauthereau
authors.forename: Cynthia
authors.initials: C
authors.lastname: Camacho-Muñoz
authors.forename: Carolina
authors.initials: C
authors.lastname: López-Rubalcava
authors.forename: Robert L
authors.initials: RL
authors.lastname: Balster
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D013287:Illicit Drugs / Q000633:toxicity; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016202:N-Methylaspartate / Q000633:toxicity; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D012997:Solvents / Q000627:therapeutic use; D013997:Time Factors; D014050:Toluene / Q000627:therapeutic use*; D014240:Trichloroethanes / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D018690:Excitatory Amino Acid Agonists; D013287:Illicit Drugs; D012997:Solvents; D014240:Trichloroethanes; C024566:1,1,1-trichloroethane; D014050:Toluene; D016202:N-Methylaspartate