Von Lubitz D K, Beenhakker M, Lin R C, Carter M F, Paul I A, Bischofberger N, Jacobson K A
NIH/NIDDK, Molecular Recognition Section, Bethesda, MD 20892 USA.
Eur J Pharmacol. 1996 Apr 29;302(1-3):43-8. doi: 10.1016/0014-2999(96)00101-x.
Agonists of adenosine A1 receptors have been frequently proposed as candidates for clinical development in treatment of cerebral ischemia and stroke. Numerous experimental studies have shown that pre- and postischemic administration of these drugs results in a very significant reduction of postischemic brain damage. However, only a few studies determined the impact of cerebral ischemia and drug treatment on postischemic recovery of spatial memory. The present paper demonstrates that preischemic i.p. administration of adenosine amine congener (ADAC) at 100 micrograms/kg in gerbils results in a significant (P < 0.05) reduction of postischemic mortality and hippocampal, cortical and striatal morbidity. Postischemic Morris' water maze tests show that preischemic treatment with ADAC also leads to a very significant (P < 0.001) reduction of postischemic spatial memory loss. Our results indicate feasibility of further consideration of adenosine A1 receptor agonists as a clinically applicable acute treatment of brain ischemia. Recent development of neuroprotective adenosine A1 receptor agonists that are free of cardiovascular side effects supports such development.
腺苷A1受体激动剂经常被提议作为治疗脑缺血和中风临床开发的候选药物。大量实验研究表明，在缺血前后给予这些药物可使缺血后脑损伤显著减轻。然而，只有少数研究确定了脑缺血和药物治疗对缺血后空间记忆恢复的影响。本文表明，在沙土鼠中，缺血前腹腔注射100微克/千克的腺苷胺类似物（ADAC）可使缺血后死亡率以及海马、皮质和纹状体发病率显著降低（P<0.05）。缺血后莫里斯水迷宫试验表明，缺血前用ADAC治疗也可使缺血后空间记忆丧失显著减轻（P<0.001）。我们的结果表明，进一步考虑将腺苷A1受体激动剂作为脑缺血的临床适用急性治疗方法具有可行性。近期开发的无心血管副作用的神经保护性腺苷A1受体激动剂支持这一开发。
