Schmidt M, Imbs J L, Neumeyer J L, Giesen E M, Schwartz J
Eur J Pharmacol. 1984 Jan 13;97(1-2):75-85. doi: 10.1016/0014-2999(84)90514-4.
The renal vascular effects of aporphines and related compounds were studied on the isolated perfused rat kidney in the presence of 10(-5) M phenoxybenzamine and 10(-5) M sotalol and after contraction of the vascular bed with prostaglandin F2 alpha (10(-7) -3 X 10(-6) M). Under these conditions, (R)-(-)-apomorphine showed renal dopaminomimetic activity, i.e. renal vasodilation competitively inhibited by (+)-butaclamol (10(-8) M) but not by (-)-butaclamol (3 X 10(-8) M). It had an apparent affinity 25 times higher but a markedly lower intrinsic activity than dopamine. N-n-Propyl and trihydroxylated aporphines were less potent and the mono-10-hydroxylated aporphine was completely inactive. (S)-(+)-Bulbocapnine also showed weak dopaminomimetic activity but tetrahydropapaveroline was devoid of such an effect. (-)-N-(2-Chloroethyl)-norapomorphine (10(-5) M) irreversibly antagonised dopamine-induced renal vasodilation. At concentrations above 3 X 10(-6) M, most aporphines and tetrahydropapaveroline induced additional non-dopamine receptor related renal vasodilation.
在存在10⁻⁵M酚苄明和10⁻⁵M索他洛尔的情况下，以及在用前列腺素F2α（10⁻⁷ - 3×10⁻⁶M）使血管床收缩后，研究了阿朴啡及其相关化合物对离体灌注大鼠肾脏的肾血管作用。在这些条件下，（R）-（-）-阿扑吗啡表现出肾多巴胺模拟活性，即肾血管舒张被（+）-布他拉莫（10⁻⁸M）竞争性抑制，但不被（-）-布他拉莫（3×10⁻⁸M）抑制。它的表观亲和力比多巴胺高25倍，但内在活性明显较低。N-正丙基和三羟基化阿朴啡的效力较低，而单-10-羟基化阿朴啡则完全无活性。（S）-（+）-紫堇碱也表现出较弱的多巴胺模拟活性，但四氢罂粟碱没有这种作用。（-）-N-（2-氯乙基）-去甲阿扑吗啡（10⁻⁵M）不可逆地拮抗多巴胺诱导的肾血管舒张。在浓度高于3×10⁻⁶M时，大多数阿朴啡和四氢罂粟碱会诱导额外的与多巴胺受体无关的肾血管舒张。
