General pharmacological profile and effects of E-4716, a novel histamine receptor blocker, on the central nervous system.

The general pharmacological profile and effects of E-4716 on the CNS have been investigated in comparison with other histamine receptor blockers. In in vitro studies with isolated organs and in binding studies on numerous receptors, E-4716 had no activity even at high concentrations, except for the selective blockade of H 1 receptors. No activity was observed in pharmacological trials in vivo, such as the Irwin test or analgesia induced by phenylbenzoquinone or electroshock suggesting a depressant activity on the CNS. In tests potentiating hypnosis induced by barbiturates, benzodiazepines and ethanol in mice, E-4716 always showed milder potentiating effects than the other reference drugs. In monkeys, no sedating effects were observed at 200 mg/kg, p.o. These results suggest that E-4716 exhibits good clinical efficacy without any secondary effects.