Influence of the antidepressant binodaline on biogenic amine uptake and brain levels in the rat.

The influence of 1-(omega-dimethylaminoethylmethyl)-amino-3-phenylindole hydrochloride (binodaline, Sgd-Scha 1059) on the uptake of noradrenaline (norepinephrine, NA), 5-hydroxytryptamine (5-HT) and dopamine (DA) into pre-synaptic nerve endings has been studied using purified synaptosomal preparations from various regions of rat brain. Binodaline was found to be an effective inhibitor of biogenic amine uptake the IC50 values being 5.0 X 10(-6) mol/l (NA), 2.3 X 10(-7) mol/l (5-HT) and 1.5 X 10(-6) mol/l (DA). The desmethyl analogue of binodaline (Sgd 20578) also inhibited transmitter uptake into cerebral nerve endings, being more potent than the parent compound in inhibiting NA uptake (8.5 X 10 mol/l), of a similar potency with respect to 5-HT (3.2 X 10(-7) mol/l) and slightly less potent against DA (8.3 X 10(-6) mol/l). Neither binodaline nor the desmethyl derivative was found to influence cerebral levels of NA, 5-HT and DA following acute dosing in rats. Brain concentrations of the related metabolites 5-hydroxyindolacetic acid, dihydroxyphenylacetic acid and homovanillinic acid were also unchanged. It is concluded that binodaline owes its antidepressant activity at least in part to its ability to inhibit monoamine uptake into pre-synaptic cerebral nerve endings.