Panchenko L F, Brusov O S, Balashov A M, Grinevich V P, Ostrovskiĭ Iu M
Vopr Med Khim. 1982 Sep-Oct;28(5):88-92.
Using the method of competitive displacement of 3H-labelled naloxone, (D-ala2)-met enkephalinamide or (D-ala2)-D-leu-enkephalin by salsolinol, 1-methyl-6-hydroxy-1, 2, 3, 4-tetrahydro-beta-carboline or 1-methyl-6-methoxy-1, 2, 3, 4-tetrahydro-beta-carboline from opiate receptors, it was shown that the alkaloids studied were capable to cause specific interactions with rat hypothalamus and midbrain however, exhibiting distinctly less affinity as compared with morphine or its analogs. The sodium ratios, determined from the effective doses of the tetrahydroisoquinoline alkaloids corresponding to the alkaloid concentrations, which induce 50% displacement of 3H-naloxone from the opiate receptors in the presence or absence of 100 mM NaCl, have been found to be 0.75 for salsolinol and 3.6 for beta-carbolines studied. The data obtained suggest that salsolinol, similar to naloxone, is a "pure" morphine antagonist, whereas the beta-carbolines studied may be classified with the agonist-antagonist type. A considerable decrease in the affinity of mu-type opiate receptors has been found in presence of salsolinol in the incubation medium. The possible mechanisms of pharmacological action of the alkaloids and their relation to development of alcohol dependence and tolerance are discussed.
采用3H标记的纳洛酮、（D-ala2）-甲硫氨酸脑啡肽酰胺或（D-ala2）-D-亮氨酸脑啡肽被盐穗木醇、1-甲基-6-羟基-1,2,3,4-四氢-β-咔啉或1-甲基-6-甲氧基-1,2,3,4-四氢-β-咔啉从阿片受体竞争性置换的方法，结果表明，所研究的生物碱能够与大鼠下丘脑和中脑发生特异性相互作用，然而，与吗啡或其类似物相比，其亲和力明显较低。根据在存在或不存在100 mM NaCl的情况下诱导3H-纳洛酮从阿片受体50%置换的生物碱浓度对应的四氢异喹啉生物碱的有效剂量确定的钠比率，已发现盐穗木醇为0.75，所研究的β-咔啉为3.6。获得的数据表明，盐穗木醇与纳洛酮类似，是一种“纯”吗啡拮抗剂，而所研究的β-咔啉可能属于激动剂-拮抗剂类型。在孵育培养基中存在盐穗木醇的情况下，已发现μ型阿片受体的亲和力显著降低。讨论了生物碱药理作用的可能机制及其与酒精依赖和耐受性发展的关系。
