Antagonism of AP-5-induced sniffing stereotypy links umespirone to atypical antipsychotics.
Blockade of glutamatergic transmission in the striatum (using the NMDA-antagonist DL-2-amino-5-phosphonovaleric acid AP-5) was recently shown to induce stereotyped sniffing in rats. Comparable stereotyped behaviour is well known to be elicited by stimulation of dopamine activity, which since long was the basis for experimental models to check for possible antipsychotic activity of new compounds. However, whereas dopamine-induced stereotypies are antagonized only by classical neuroleptics, stereotypies induced by blockade of glutamatergic transmission are antagonized by classical as well as by atypical antipsychotics. Umespirone, a novel psychotropic which has been reported to exhibit behavioural effects predictive for antipsychotic as well as anxiolytic potential was evaluated for antagonistic effects against AP-5-induced behaviour. The profile of umespirone was compared with the profile of a non-benzodiazepine anxiolytic buspirone as well as with previously published data of neuroleptics. Umespirone like clozapine specifically antagonized AP-5-induced sniffing, i.e. did not impair spontaneous sniffing but reversed AP-5-induced excessive sniffing. In contrast, buspirone impaired spontaneous and AP-5-induced sniffing to about the same extend. These results are in accordance with the glutamate hypothesis of schizophrenia and again give evidence that umespirone should have antipsychotic potential and a very low liability to exhibit unspecific sedative action.
Schmidt
W J
WJ
Universität Tübingen, Abt. Neuropharmakologie, F.R.G.
Krähling
H
H
Ruhland
M
M
D015763:2-Amino-5-phosphonovalerate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002065:Buspirone / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D009812:Odorants; D051381:Rats; D011919:Rats, Inbred Strains; D013239:Stereotyped Behavior / Q000187:drug effects*; D013329:Structure-Activity Relationship
D014150:Antipsychotic Agents; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D015763:2-Amino-5-phosphonovalerate; C059363:umespirone; D003024:Clozapine; D002065:Buspirone