title: Demonstration of the partial agonist profiles of Ro 16-6028 and Ro 17-1812 in mice in vivo.
abstract: Benzodiazepine receptor occupancy by the full agonist, diazepam, and by the two putative partial agonists, Ro 16-6028 and Ro 17-1812, was measured by inhibition of in vivo [3H]Ro 15-1788 binding in mouse brain and was correlated with their pharmacological effects. The anticonvulsant effects of Ro 16-6028, Ro 17-1812 and diazepam (ED50 values) appeared at receptor occupancies of 40, 20 and less than 5%, respectively. Moreover, at the highest measurable receptor occupancy (90-100%), Ro 16-6028 and Ro 17-1812 did not induce any rotarod deficit whereas a complete deficit was observed with diazepam at 35% receptor occupancy.
authors.affiliation: Laboratoire de Physiologie Nerveuse, C.N.R.S., Gif-sur-Yvette, France.
authors.forename: M C
authors.initials: MC
authors.lastname: Potier
authors.forename: L
authors.initials: L
authors.lastname: Prado de Carvalho
authors.forename: P
authors.initials: P
authors.lastname: Venault
authors.forename: G
authors.initials: G
authors.lastname: Chapouthier
authors.forename: J
authors.initials: J
authors.lastname: Rossier
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001259:Ataxia / Q000139:chemically induced; D001570:Benzodiazepinones / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D003220:Conflict, Psychological; D003975:Diazepam / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors; D011963:Receptors, GABA-A / Q000187:drug effects
chemical_list: D000927:Anticonvulsants; D001570:Benzodiazepinones; D011963:Receptors, GABA-A; C049715:Ro 17-1812; C054626:bretazenil; D003975:Diazepam; D010433:Pentylenetetrazole