Structure-activity relationship for the anticonvulsant effects of organic solvents

Abstract

Several organic solvents have anticonvulsant or convulsant actions depending on the dose and exposure time. To study if there is a structure-activity relationship for organic solvents as anticonvulsant agents we subjected independent groups of mice to a single 30-min exposure session to inhale n-hexane, cyclohexane, benzene (8000ppm each), toluene (500-6000ppm), m-xylene (1000-6000ppm), ethylbenzene (500-4000ppm) or propylbenzene (500-4000ppm). Immediately after, animals were injected i.p. with 90mg/kg pentylenetetrazol (PTZ) and re-exposed to the same solvent for another 30min. During this time, the occurrence of seizures and death was recorded. n-Hexane and cyclohexane had no anticonvulsant effect. Benzene and alkylbenzenes delayed the onset of PTZ-induced seizures. In addition, all four alkylbenzenes decreased the number of animals that seized. Propylbenzene and ethylbenzene were equally effective, but more potent than toluene and m-xylene to block PTZ actions. In the second part of the study we exposed independent groups of mice to 8000ppm n-hexane, cyclohexane (solvents without effect in the PTZ experiment), 8000ppm benzene or 6000ppm toluene, m-xylene, ethylbenzene or propylbenzene following the same experimental protocol (i.e. 30-min exposure, injection, 30-min re-exposure), but using 120mg/kg NMDA as the convulsant agent. All aromatic compounds prevented NMDA lethal effects, but only benzene and toluene decreased the percentage of animals that seized. Taken together, our data suggest that the benzene ring alone or substituted with alkyl groups is necessary for the anticonvulsant effect of acute solvent exposure against seizures and/or death produced by PTZ or NMDA.

Keywords: Alkylbenzenes; Death; Inhalants; NMDA; PTZ; Seizures.