Kulinskiĭ V I, Gavrilov S S
Eksp Klin Farmakol. 2006 Nov-Dec;69(6):20-3.
Selective dopamine (D) receptor agonists either slightly improve (D2 and D3) or do not affect (D1 and D4) the tolerance of the brain to global ischemia. As for D and 5-HT (hydroxytryptamine) antagonists, only D1 antagonist SCH 23390 and 5-HT2 antagonist ketanserin produce a small neuroprotective effect, while D2, D4, 5-HT(2B) and 5-HT(2C) antagonists are not active. Simultaneous injection of D2 (raclopride), D3 (GR 103691), and D4 (L 745870) receptor blockers also does not protect the brain. These results are not at variance with a widespread hypothesis that the accumulation of extracellular 5-HT and especially D in the brain causes the neuron damage. The effect of ketanserine is not increased by D2 or D4 blockers, but the introduction of D3 blocker GR 103691 (+88%) and especially the simultaneous injection of D2,3,4 antagonists improve the effect of ketanserine (+134%). The neuroprotective effect of the last combination is not lower but even exceeds that of some neuroleptics. This fact shows the possibility to increase the tolerance to cerebral ischemia by simultaneously blocking D and 5-HT-receptors.
选择性多巴胺（D）受体激动剂对大脑全脑缺血耐受性的影响，要么是轻微改善（D2和D3受体激动剂），要么无影响（D1和D4受体激动剂）。至于D受体和5-羟色胺（5-HT）拮抗剂，只有D1拮抗剂SCH 23390和5-HT2拮抗剂酮色林具有较小的神经保护作用，而D2、D4、5-HT（2B）和5-HT（2C）拮抗剂则无活性。同时注射D2（雷氯必利）、D3（GR 103691）和D4（L 745870）受体阻滞剂也不能保护大脑。这些结果与一种广泛的假设并不矛盾，即大脑中细胞外5-羟色胺尤其是多巴胺的积累会导致神经元损伤。酮色林的作用不会因D2或D4受体阻滞剂而增强，但引入D3受体阻滞剂GR 103691（增加88%），尤其是同时注射D2、3、4受体拮抗剂可增强酮色林的作用（增加134%）。最后这种组合的神经保护作用不低于甚至超过某些抗精神病药物。这一事实表明，通过同时阻断D受体和5-羟色胺受体有可能提高对脑缺血的耐受性。
