title: General pharmacological profile and effects of E-4716, a novel histamine receptor blocker, on the central nervous system.
abstract: 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 H1 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.
authors.affiliation: Laboratorios Dr. Esteve, S.A., Barcelona, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Fisas
authors.forename: B
authors.initials: B
authors.lastname: Gutiérrez
authors.forename: M
authors.initials: M
authors.lastname: Fort
authors.forename: A
authors.initials: A
authors.lastname: Dordal
authors.forename: C
authors.initials: C
authors.lastname: García
authors.forename: A J
authors.initials: AJ
authors.lastname: Farré
mesh_terms: D000818:Animals; D001463:Barbiturates / Q000494:pharmacology; D001562:Benzimidazoles / Q000378:metabolism / Q000494:pharmacology*; D002490:Central Nervous System / Q000187:drug effects*; D002707:Chlordiazepoxide / Q000494:pharmacology; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D011817:Rabbits; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D001463:Barbiturates; D001562:Benzimidazoles; C104131:E 4716; D006634:Histamine H1 Antagonists; D011956:Receptors, Cell Surface; D000431:Ethanol; D002707:Chlordiazepoxide