The effects of umespirone as a potential anxiolytic and antipsychotic agent.
Umespirone was compared to buspirone, diazepam and clozapine as a potential anxiolytic and antipsychotic agent. In the mouse black and white test box, umespirone was considerably more potent than diazepam or buspirone to reduce aversive responding, tolerance to its effects was not observed and sedation was absent, a chronic treatment and withdrawal was not associated with an anxiogenic profile, and umespirone prevented the behavioural consequences of withdrawal from diazepam. Umespirone also had an anxiolytic profile of action in the tests of rat social interaction and in the marmoset exposed to a human threat. Both umespirone and clozapine reduced the hyperactivity induced by the infusion of dopamine into the nucleus accumbens of rat. In radioligand binding assays umespirone demonstrated nanomolar affinity for the alpha 1-adrenoceptor and the 5-HT1A and dopamine D2 receptors. It is concluded that umespirone may present as a novel psychotropic agent with anxiolytic and antipsychotic potential.
School of Pharmacy, University of Bradford, West Yorkshire, UK.
N M
NM
Barnes
B
B
Costall
A M
AM
Domeney
P A
PA
Gerrard
M E
ME
Kelly
H
H
Krähling
R J
RJ
Naylor
D M
DM
Tomkins
T J
TJ
Williams
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002065:Buspirone / Q000494:pharmacology; D002144:Callithrix; D003024:Clozapine / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology; D005260:Female; D007398:Interpersonal Relations; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains; D011955:Receptors, Drug / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D014150:Antipsychotic Agents; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011955:Receptors, Drug; D013764:Tetrahydronaphthalenes; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C059363:umespirone; D003024:Clozapine; D003975:Diazepam; D002065:Buspirone; D004298:Dopamine