Hava M, Bernstein J, Smissman E E, El-Antably S
J Med Chem. 1976 Jan;19(1):52-4. doi: 10.1021/jm00223a011.
Two N-isopropylnorephedrines and their four possible decalol analogs were compared pharmacologically. Four of the six compounds at a concentration of 1 x 10(-4) M caused a potentiation of D(-)-norepinephrine (NE) contraction of the rat vas deferens and increased the maximal response of the preparation to NE. Pretreatment in vivo with reserpine (5 mg/kg ip) 24 hr before the experiment in vitro did not change these effects. At a concentration higher than 1 x 10(-3) M all of the decalin analogs antagonized the effects of NE. All of the analogs lowered the dog blood pressure briefly. The lowering of blood pressure was augmented by alpha-adrenergic blockade and was not changed by beta-adrenergic blockade, atropine, or a ganglionic blocking agent. Tachyphylaxis was not observed. The spontaneous contraction of isolated rabbit atria was depressed by the substances at concentrations of 1 x 10(-4)-1 x 10(-3) M. Catecholamine uptake in rat vas deferens was lowered by the substances and all of them produced a release of catecholamines from vas deferens. By virtue of the conformational rigidity of the decalols, possible inferences concerning the stereochemical aspects of the interaction of the ephedrine analogs with adrenergic neurone-receptor sites are discussed.
对两种N-异丙基去甲麻黄碱及其四种可能的十氢化萘类似物进行了药理学比较。六种化合物中的四种在浓度为1×10⁻⁴ M时可增强大鼠输精管对D-（-）-去甲肾上腺素（NE）的收缩作用，并增加该制剂对NE的最大反应。在体外实验前24小时腹腔注射利血平（5 mg/kg）进行体内预处理，并未改变这些作用。当浓度高于1×10⁻³ M时，所有十氢化萘类似物均拮抗NE的作用。所有类似物均使犬血压短暂降低。α-肾上腺素能阻断可增强血压降低作用，而β-肾上腺素能阻断、阿托品或神经节阻断剂对此无影响。未观察到快速耐受性。在浓度为1×10⁻⁴ - 1×10⁻³ M时，这些物质可抑制离体兔心房的自发收缩。这些物质可降低大鼠输精管中的儿茶酚胺摄取，并且它们均可使输精管释放儿茶酚胺。借助十氢化萘的构象刚性，讨论了有关麻黄碱类似物与肾上腺素能神经元-受体部位相互作用的立体化学方面的可能推断。
