Ostrovskaia R U
Biull Eksp Biol Med. 1984 Oct;98(10):436-9.
Neuropharmacological analysis of previously revealed antihypoxic activity of benzodiazepines (BDZ) has been performed in experiments on mice exposed to hypoxia. Antihypoxic effect of diazepam is shown to be antagonized by the central BDZ receptor blocker, Ro 15-1788. A certain degree of antihypoxic activity also abolished by Ro 15-1788 is exhibited by hypothetical ligands of BDZ receptors: inosin, nicotinamide, ethyl-beta-carboline-3-carboxylate. The effect of dipyridamole, a drug with high affinity for BDZ receptors of the peripheral type is not antagonized by Ro 15-1788, another evidence of Ro 15-1788 affinity precisely to the central BDZ receptors. GABA-mimetics (muscimol and GABA cetyl ester) were also found to have marked antihypoxic activity. Unlike BDZ receptor agonists, this effect is reduced by bicuculline and not by Ro 15-1788. The data obtained suggest that antihypoxic activity of BDZ is caused by their direct interaction with the central BDZ receptors, probably with the type which is not modulated by GABAA receptors.
在暴露于低氧环境的小鼠实验中，对先前揭示的苯二氮䓬类药物（BDZ）的抗缺氧活性进行了神经药理学分析。结果表明，地西泮的抗缺氧作用可被中枢BDZ受体阻断剂Ro 15 - 1788拮抗。BDZ受体的假定配体：肌苷、烟酰胺、β - 咔啉 - 3 - 羧酸乙酯也表现出一定程度的抗缺氧活性，且该活性也被Ro 15 - 1788消除。外周型BDZ受体高亲和力药物双嘧达莫的作用不被Ro 15 - 1788拮抗，这是Ro 15 - 1788精确作用于中枢BDZ受体的另一证据。还发现GABA模拟物（蝇蕈醇和GABA十六烷基酯）具有显著的抗缺氧活性。与BDZ受体激动剂不同，这种作用可被荷包牡丹碱降低，而不是被Ro 15 - 1788降低。所得数据表明，BDZ的抗缺氧活性是由它们与中枢BDZ受体的直接相互作用引起的，可能与不受GABAA受体调节的类型有关。
