The selective dopamine antagonist properties of BRL 34778: a novel substituted benzamide.
BRL 34778, exo-4-amino-5-chloro-2-methoxy-N-[9-(4-fluorophenylmethyl)-9-azabi cyclo(3.3.1) non-3-yl]-benzamide, is a very potent and specific dopamine D2-receptor antagonist. It exhibits a Ki value of 2.14 nM for dopamine D2-receptors but much lower affinity for D1-(Ki 5700 nM) and for many other receptor types. Its action is potent and of long duration in models for antipsychotic activity (4 h ED50s PO are 0.017 mg/kg for antagonism of apomorphine-induced climbing in mice and 0.028 mg/kg for antagonism of amphetamine-induced locomotion in rats). In contrast to its high potency in models for antipsychotic activity, BRL 34778 is much weaker in models for extrapyramidal effects and sedation (4 h ED50s PO are 2.4 mg/kg for inducing catalepsy in rats and 1.14 mg/kg for inhibition of rearing behaviour in rats). These data indicate potent activity of BRL 34778 in models for antipsychotic activity but low activity in models for extrapyramidal effects and sedation.
D000067956:Adenylyl Cyclase Inhibitors; D000661:Amphetamine / Q000037:antagonists & inhibitors; D000818:Animals; D001058:Apomorphine / Q000037:antagonists & inhibitors; D001362:Avoidance Learning / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology*; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002375:Catalepsy / Q000139:chemically induced; D004285:Dogs; D018492:Dopamine Antagonists; D004569:Electroencephalography; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011388:Prolactin / Q000097:blood; D051381:Rats; D012919:Social Behavior
D000067956:Adenylyl Cyclase Inhibitors; D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D018492:Dopamine Antagonists; C055484:BRL 34778; D011388:Prolactin; D000661:Amphetamine; D001058:Apomorphine