Benfield D P, Luscombe D K
Arzneimittelforschung. 1983;33(6):847-50.
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.
利用从大鼠脑不同区域纯化得到的突触体标本，研究了1-（ω-二甲基氨基乙基甲基）-氨基-3-苯基吲哚盐酸盐（双节点林，Sgd-Scha 1059）对去甲肾上腺素（去甲肾腺素，NA）、5-羟色胺（5-HT）和多巴胺（DA）摄入突触前神经末梢的影响。发现双节点林是生物胺摄取的有效抑制剂，其IC50值分别为5.0×10⁻⁶mol/L（NA）、2.3×10⁻⁷mol/L（5-HT）和1.5×10⁻⁶mol/L（DA）。双节点林的去甲基类似物（Sgd 20578）也抑制递质摄入脑神经末梢，在抑制NA摄取方面比母体化合物更有效（8.5×10⁻⁸mol/L），对5-HT的效力相似（3.2×10⁻⁷mol/L），对DA的效力略低（8.3×10⁻⁶mol/L）。在对大鼠急性给药后，未发现双节点林及其去甲基衍生物影响脑内NA、5-HT和DA的水平。相关代谢产物5-羟吲哚乙酸、二羟基苯乙酸和高香草酸的脑内浓度也未改变。结论是双节点林的抗抑郁活性至少部分归因于其抑制单胺摄入突触前脑神经末梢的能力。
