In vivo interaction of zolpidem with central benzodiazepine (BZD) binding sites (as labeled by [3H]Ro 15-1788) in the mouse brain. Preferential affinity of zolpidem for the omega 1 (BZD1) subtype.
Zolpidem is a novel hypnotic drug which possesses preferential affinity, under in vitro conditions, for the omega 1 (BZD1) subtype of BZD binding sites. In the present study the in vivo interaction of zolpidem with mouse brain BZD binding sites, as labeled by i.v. injection of [3H]Ro 15-1788, has been investigated. Intraperitoneal administration of zolpidem (30 min before sacrifice) decreased in a dose-dependent manner, the retention of [3H]Ro 15-1788 in the cerebral cortex (ED50 = 8.9 mg/kg i.p.); the inhibition by zolpidem was maximal (70%) at 5 to 10 min postinjection and of only 10% 1 hr later. These kinetics are in agreement with its short lasting hypnotic properties. CGS 9896, CL 218,872 and flunitrazepam also prevented the cortical accumulation of [3H]Ro 15-1788 with ED50 values of 12.5, 24 and 0.17 mg/kg i.p., respectively. Zolpidem, like flunitrazepam, diminishes exploratory activity and possesses anticonvulsant and myorelaxant effects in the mouse. However, in contrast to flunitrazepam, the sedative action of zolpidem can be evidenced at a much lower recognition site occupancy (35%) than that needed for myorelaxant or anticonvulsant effects (50-56%). The regional selectivity of zolpidem as an inhibitor of [3H]Ro 15-1788 in vitro and in vivo binding in the mouse brain has been assessed by quantitative autoradiography.(ABSTRACT TRUNCATED AT 250 WORDS)
Benavides
J
J
Laboratoires d'Etudes et de Recherches Synthélabo, Bagneux, France.
Peny
B
B
Dubois
A
A
Perrault
G
G
Morel
E
E
Zivkovic
B
B
Scatton
B
B
D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D005442:Flumazenil / Q000378:metabolism*; D005445:Flunitrazepam / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D011724:Pyridazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D000077334:Zolpidem
D006993:Hypnotics and Sedatives; D011724:Pyridazines; D011725:Pyridines; D011963:Receptors, GABA-A; D005442:Flumazenil; D005445:Flunitrazepam; C021604:CL 218872; D000077334:Zolpidem