The potential anxiolytic activity of GR38032F, a 5-HT3-receptor antagonist.
1. The highly selective 5-HT3-receptor antagonist, GR38032F, has been tested in five animal models predictive for anxiolytic activity. 2. In the social interaction test in the rat and in a light/dark exploration test in the mouse, GR38032F dose-dependently released suppressed behaviour without modifying locomotor activity. 3. In the cynomolgus monkey and the marmoset, GR38032F reduced anxiety-related symptoms without causing sedation. In the marmoset, the effects were clearly dose-related. 4. GR38032F did not have any detectable activity in the water-lick conflict test in the rat. 5. We conclude that GR38032F is potentially a very potent anxiolytic agent without sedative, anticonvulsant or hypnotic activity.
D000818:Animals; D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D002143:Callitrichinae; D003220:Conflict, Psychological; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D017294:Ondansetron; D010424:Pentobarbital / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors; D011869:Radioligand Assay; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects*; D012890:Sleep / Q000187:drug effects
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D007093:Imidazoles; D011985:Receptors, Serotonin; D017294:Ondansetron; D010424:Pentobarbital; D010433:Pentylenetetrazole