Chloroethylnorapomorphine, a proposed long-acting dopamine antagonist: interactions with dopamine receptors of mammalian forebrain in vitro.
N-Chloroethylnorapomorphine (NCA) interacts with homogenates of rat corpus striatum to block subsequent stimulation of cyclic AMP synthesis by 50 micro M dopamine (DA) (IC50 30 micro M). The 10-O-methylated (11-monophenolic) analog of NCA is weaker; an O,O'-diester of NCA is inactive. The NCA-induced inhibition is counteracted by coincubation with DA or apomorphine, but not norepinephrine. Blockade by NCA is non-competitive vs. DA and not readily reversed by washing. NCA also competes for binding of 3H-apomorphine to subsynaptosomal calf caudate membranes (IC50 285 nM) with greater potency than the monophenolic or diester analogs. NCA may represent a unique long-acting antagonist of DA receptors.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000378:metabolism; D001060:Aporphines / Q000494:pharmacology*; D002417:Cattle; D003342:Corpus Striatum / Q000187:drug effects*; D066298:In Vitro Techniques; D010643:Phenoxybenzamine / Q000378:metabolism; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*
D001060:Aporphines; D011954:Receptors, Dopamine; D010643:Phenoxybenzamine; C025935:chloroethylnorapomorphine; D000262:Adenylyl Cyclases; D001058:Apomorphine