Demonstration of the partial agonist profiles of Ro 16-6028 and Ro 17-1812 in mice in vivo.
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.
Potier
M C
MC
Laboratoire de Physiologie Nerveuse, C.N.R.S., Gif-sur-Yvette, France.
Prado de Carvalho
L
L
Venault
P
P
Chapouthier
G
G
Rossier
J
J
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
D000927:Anticonvulsants; D001570:Benzodiazepinones; D011963:Receptors, GABA-A; C049715:Ro 17-1812; C054626:bretazenil; D003975:Diazepam; D010433:Pentylenetetrazole