Influence of histamine and related compounds on the hypnotic effect of thiopental in mice.

Abstract

Intraventricular injection of histamine (Hi) significantly prolonged thiopental sleeping time at doses of 0.5μg or larger. Both 1-methylHi and imidazole-4-acetic acid, howere, did not affect thiopental narcosis. Pretreatment with α-fluoromethylhistidine diminished the effect of Hi, while histidine, metoprine and quinacrine prolonged thiopental narcosis. Injection with 2-methylHi did not affect thiopental sleeping time, while as in the case of Hi, 4-methylHi augmented the thiopental effect. In addition, H₂-receptor blocking agents such as cimetidine, ranitidine and famotidine clearly antagonized Hi-induced prolongation of thiopental narcosis, while pyrilamine and chlorpheniramine had no effect. These results indicate that Hi-induced prolongation of thiopental narcosis appears to be exerted via H₂ receptors and is, in some way, related to the Hi content in the brain.