Carisoprodol pharmacokinetics and distribution in the nucleus accumbens correlates with behavioral effects in rats independent from its metabolism to meprobamate

Carisoprodol produces behavioral effects in rats that track carisoprodol brain and blood levels, not the levels of its active metabolite meprobamate. Rats were trained in a drug discrimination paradigm to distinguish carisoprodol, and researchers compared the timing of drug-appropriate responding with pharmacokinetics measured using in vivo microdialysis from blood and the nucleus accumbens. The discriminative stimulus time course matched carisoprodol concentrations in blood and nucleus accumbens. Blocking carisoprodol metabolism to meprobamate with the cytochrome P450 inhibitor cimetidine increased carisoprodol and decreased meprobamate levels, but did not change carisoprodol’s discriminative stimulus effects. The findings support a direct central action of carisoprodol and imply that understanding its mechanism independently of meprobamate matters for clinical use and abuse liability.