Ponzio F, Algeri S, Garattini S, Cioce V, Rusconi L, Sacchetti G, Manuel C, Notelle C, Duvert L, Legeai J
Istituto di Richerche Farmacologiche Mario Negri, Milan, Italy.
Pharmacol Res Commun. 1987 Aug;19(8):555-65. doi: 10.1016/0031-6989(87)90093-2.
6-Methylamino-4,5,6,7-tetrahydrobenzothiazole monochlorhydrate (14.839JL) is a new, potent dopaminergic agonist. The stereotypy induced by this drug was greater than that induced by an equivalent dose of apomorphine, was antagonized by pretreatment with sulpiride and counteracted the hypomotility induced by reserpine. Striatal levels of the dopamine metabolites homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC) and 3-methoxytyramine (3-MT) were significantly lowered for up to 4-6 h by doses from 0.05 to 1 mg/kg. The drug was also very effective in lowering prolactine secretion. 14.839JL displaced [3H]N-n-propylnorapomorphine [3H]NPA from striatal binding sites with an IC50 similar to dopamine (DA). Conversely, the ability of 14.839JL to displace 3H spiperone from its binding sites was 100 and 10 times lower than that of haloperidol and sulpiride, and similar to that of SCH 23390. Differently from the latter, however, 14.839JL did not modify adenylate cyclase activity. All these data suggest that 14.839JL is a new, potent, long-lasting direct DA agonist, probably acting on D2 receptors.
6-甲基氨基-4,5,6,7-四氢苯并噻唑盐酸盐（14.839JL）是一种新型强效多巴胺能激动剂。该药物诱导的刻板行为比同等剂量的阿扑吗啡诱导的更强烈，可被舒必利预处理拮抗，并能对抗利血平诱导的运动迟缓。剂量为0.05至1mg/kg时，纹状体中多巴胺代谢产物高香草酸（HVA）、二羟基苯乙酸（DOPAC）和3-甲氧基酪胺（3-MT）的水平在长达4至6小时内显著降低。该药物在降低催乳素分泌方面也非常有效。14.839JL从纹状体结合位点置换[3H]N-正丙基去甲阿扑吗啡[3H]NPA的IC50与多巴胺（DA）相似。相反，14.839JL从其结合位点置换3H-螺哌隆的能力比氟哌啶醇和舒必利低100倍和10倍，与SCH 23390相似。然而，与后者不同的是，14.839JL不会改变腺苷酸环化酶活性。所有这些数据表明，14.839JL是一种新型、强效、长效的直接DA激动剂，可能作用于D2受体。
