Antagonism of AP-5- and amphetamine-induced behaviour by timelotem as compared with clozapine and haloperidol.
Bilateral intrastriatal injection of DL-2-amino-5-phosphonovaleric acid (AP-5), that blocks glutamatergic transmission at the N-methyl-d-aspartate preferring receptor, induces sniffing and body turns and reduces grooming in rats. Timelotem, a representative of the newly developed chemical class of anellated benzodiazepines antagonized specifically AP-5-induced sniffing and body turns. Classical (haloperidol) as well as atypical (clozapine) neuroleptics had recently been shown to antagonize AP-5-induced sniffing; clozapine, like timelotem, but not haloperidol, additionally antagonized AP-5-induced body turns. Further, timelotem antagonized amphetamine-induced stereotyped behaviour in rats, but was found less active than haloperidol in this test. Comparing the activity of drugs in both paradigms revealed that haloperidol inhibited AP-5-induced sniffing and amphetamine-induced stereotypies within the same dose range, but timelotem and clozapine were found more potent in the AP-5 test than in the amphetamine test. Thus, detailed drug profiles discriminate timelotem and clozapine from haloperidol, linking timelotem again to atypical antipsychotic compounds.
D015763:2-Amino-5-phosphonovalerate; D000661:Amphetamine / Q000037:antagonists & inhibitors*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001569:Benzodiazepines / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology*; D003984:Dibenzazepines / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
D003984:Dibenzazepines; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; C053840:timelotem; D001569:Benzodiazepines; D015763:2-Amino-5-phosphonovalerate; D000661:Amphetamine; D014633:Valine; D003024:Clozapine; D006220:Haloperidol