Novel non-benzodiazepine anxiolytics.
Several new non-benzodiazepine anxiolytics are reported. These include tracazolate, zopiclone, CL218,872, CGS9896, buspirone, MK-801 and fenobam. A comparison of anticonflict effects and propensity to cause sedation and potentiate the actions of ethanol is given as well as their effects upon the binding of [3H]flunitrazepam in vitro. Their anxiolytic properties after treatment with the benzodiazepine antagonist, RO15-1788, are reported also. Tracazolate shows a wide separation between anxiolytic activity and ability to cause sedation and to potentiate alcohol. It enhanced binding of [3H]-flunitrazepam in contrast to benzodiazepines which displace it. Buspirone was without anticonflict activity and had no effect on benzodiazepine binding while fenobam and MK-801, also without effect on binding, showed large and small differences on causing sedation and potentiating alcohol respectively. Among the displacers of [3H]flunitrazepam zopiclone showed diminished sedation liability, compared to diazepam, as did CL218,872 and CGS9896. Zopiclone caused potentiation of ethanol however, at doses close to anxiolytic doses, while CL218,872 and CGS9896 showed a wider safety margin for potentiation of ethanol compared to anxiolytic doses. The drug RO15-1788 antagonised the anticonflict effects of benzodiazepine displacers and had no effects upon the other agents studied.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D053961:Azabicyclo Compounds; D001569:Benzodiazepines / Q000037:antagonists & inhibitors; D001570:Benzodiazepinones / Q000494:pharmacology; D003220:Conflict, Psychological; D005442:Flumazenil; D005445:Flunitrazepam / Q000378:metabolism; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D051379:Mice; D010879:Piperazines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects; D011963:Receptors, GABA-A
D014151:Anti-Anxiety Agents; D053961:Azabicyclo Compounds; D001570:Benzodiazepinones; D006993:Hypnotics and Sedatives; D010879:Piperazines; D011720:Pyrazoles; D011724:Pyridazines; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; C515050:zopiclone; D001569:Benzodiazepines; D005442:Flumazenil; D005445:Flunitrazepam; C021604:CL 218872; C034704:2-(4-chlorophenyl)-2,5-dihydropyrazolo(4,3-c)quinoline-3(3H)-one; C034317:tracazolate