Anti-serotonergic effects of urethane and chloral hydrate may not be mediated by a blockade of 5-HT2 receptors

The general anesthetics urethane and chloral hydrate have profound anti-serotonergic effects both in the rat cortex in vivo and the rat aortic ring in vitro. The suggestion that these effects may be due to an action on 5-HT2 receptors was tested using ex vivo and in vitro [H-3]ketanserin binding assays with membrane-enriched fractions from rat brain. Urethane did not alter [H-3]ketanserin binding in the ex vivo assay. In the in vitro assay, urethane, chloral hydrate, and its active metabolite 2,2,2-trichloroethanol produced slight reductions (of 16%, 9%, and 18%, respectively) of [H-3]ketanserin binding. These studies suggest that anti-serotonergic effects of urethane and chloral hydrate may not be mediated by a blockade of 5-HT2 receptors.