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 μM dopamine (DA) (IC₅₀ 30 μM). The 10-O-methylated (12-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.