Schmidt M, Imbs J L, Giesen E M, Schwartz J
Eur J Pharmacol. 1982 Oct 15;84(1-2):61-70. doi: 10.1016/0014-2999(82)90157-1.
The renal vascular effects of dopaminomimetics were studied in the isolated perfused rat kidney after pretreatment with 10(-5) M phenoxybenzamine and 10(-5) M sotalol and after contraction of the vascular bed with prostaglandin F2 alpha (10(-7) to 3 x 10(-6) M). Under these conditions, our criterion for vascular dopaminomimetic activity was renal vasodilation, competitively inhibited by d-butaclamol (10(-8) M) but not by 1-butaclamol (3 x 10(-8) M). Dopamine is active at micromolar concentrations (ED50 = 2.53 +/- 0.34 x 10(-6) M). The N-alkylated analogues of dopamine preserve this activity if the alkyl group is a methyl group (epinine) or two n-propyl groups (di-n-propyl-dopamine). The catechol nucleus appears essential for renal vascular dopaminomimetic activity (SK&F 38393, active; p-tyramine, di-n-propyl-m-tyramine and RU 24926, inactive). Bromocriptine reproduces renal dopaminergic vasodilation with an ED50 of 1.3 +/- 0.14 x 10(-6) M. The study of structure-activity relationships of dopaminomimetics relates the vascular dopamine receptor, associated with renal vasodilation, to the dopamine receptor, associated with stimulation of dopamine-sensitive adenylate cyclase.
在用10⁻⁵M酚苄明和10⁻⁵M索他洛尔预处理后，以及在用前列腺素F2α（10⁻⁷至3×10⁻⁶M）使血管床收缩后，在离体灌注大鼠肾脏中研究了拟多巴胺药物的肾血管效应。在这些条件下，我们对血管拟多巴胺活性的标准是肾血管舒张，其可被d-布他拉莫（10⁻⁸M）竞争性抑制，但不被l-布他拉莫（3×10⁻⁸M）抑制。多巴胺在微摩尔浓度下具有活性（ED50 = 2.53±0.34×10⁻⁶M）。如果烷基是甲基（表灵）或两个正丙基（二正丙基多巴胺），多巴胺的N-烷基化类似物保留这种活性。儿茶酚核对于肾血管拟多巴胺活性似乎是必不可少的（SK&F 38393，有活性；对酪胺、二正丙基间酪胺和RU 24926，无活性）。溴隐亭以1.3±0.14×10⁻⁶M的ED50重现肾多巴胺能血管舒张。对拟多巴胺药物构效关系的研究将与肾血管舒张相关的血管多巴胺受体与与刺激多巴胺敏感腺苷酸环化酶相关的多巴胺受体联系起来。
