Jaen J C, Wise L D, Heffner T G, Pugsley T A, Meltzer L T
Department of Chemistry, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
J Med Chem. 1988 Aug;31(8):1621-5. doi: 10.1021/jm00403a022.
The synthesis and pharmacological properties of a novel type of [(arylpiperazinyl)alkoxy]anilines with dopaminergic properties are described. One of these compounds, 3-[3-(4-phenyl-1-piperazinyl)propoxy]benzenamine (4c), has been identified as a selective dopamine (DA) autoreceptor agonist in tests that include [3H]haloperidol binding, inhibition of striatal DA synthesis, inhibition of DA neuronal firing, inhibition of spontaneous locomotor activity, and reversal of reserpine-induced depression in rats. In addition, 4c possesses good oral activity in the Sidman conditioned avoidance test in squirrel monkeys, which is indicative of antipsychotic activity. In a primate model, 4c was found to lack the liability for extrapyramidal side effects usually associated with antipsychotic drugs.
描述了一种具有多巴胺能特性的新型[(芳基哌嗪基)烷氧基]苯胺的合成及其药理学性质。其中一种化合物，3-[3-(4-苯基-1-哌嗪基)丙氧基]苯胺(4c)，在包括[3H]氟哌啶醇结合、纹状体多巴胺合成抑制、多巴胺神经元放电抑制、自发运动活性抑制以及大鼠利血平诱导抑郁的逆转等试验中被鉴定为一种选择性多巴胺(DA)自身受体激动剂。此外，4c在松鼠猴的西德曼条件回避试验中具有良好的口服活性，这表明其具有抗精神病活性。在灵长类动物模型中，发现4c不存在通常与抗精神病药物相关的锥体外系副作用风险。
