Yasnetsov V V, Karsanova S K, Yasnetsov Vik V, Ivanov Yu V, Motin V G, Chelnaya N A
Aviakosm Ekolog Med. 2016;50(6):59-63. doi: 10.21687/0233-528x-2016-50-6-59-63.
Experiments with cats showed that microinjections into the lung of new 3-hydroxypyridine derivatives SK-119 and IBKhF-27 had a direct action on 50 and 84 % of medial vestibular nucleus (MVN) neurons respectively. The inhibitory response to the compounds was observed 6 and 25 times more frequently than exciting; inhibition by IBKhF-27 was observed 1.9 times more frequently than by SK-119. Also, microinjections of SK-1 19 and IBKhF-27 acted directly on 44 % and 81 % of cat's Purkinje cells, respectively. In case of Purkinje cells, the inhibitory reaction was seen 5.5 and 25 times oftener than exciting, respectively, and inhibition by IBKhF-27 occurred 2.1 times more frequently than by SK-119. Investigations of rat's cerebellum sections evidenced that 5 mM of IBKhF-27 inhibited population responses of Purkinje cells 95 1 3 %. In the presence of specific noncompetitive NMDA-receptor antagonist (MK-801, 100 pM) the depressive effect was annulled almost fully by 96 * 2 %. It follows that IBKhF-27 nearly entirely inhibits synaptic transmission from cerebellar parallel fibers to Purkinje cells, while MK-801 has a similarly strong anti-depression effect that testifies the involvement of the NMDA-receptor complex predominantly.
对猫进行的实验表明,向肺部微量注射新型3 - 羟基吡啶衍生物SK - 119和IBKhF - 27,分别对50%和84%的内侧前庭核(MVN)神经元有直接作用。观察到对这些化合物的抑制反应比兴奋反应频繁6倍和25倍;观察到IBKhF - 27引起的抑制比SK - 119频繁1.9倍。此外,微量注射SK - 119和IBKhF - 27分别对44%和81%的猫浦肯野细胞有直接作用。对于浦肯野细胞,抑制反应分别比兴奋反应频繁5.5倍和25倍,且IBKhF - 27引起的抑制比SK - 119频繁2.1倍。对大鼠小脑切片的研究表明,5 mM的IBKhF - 27可抑制浦肯野细胞群体反应95±3%。在存在特异性非竞争性NMDA受体拮抗剂(MK - 801,100 pM)的情况下,这种抑制作用几乎完全被消除,消除率为96±2%。由此可见,IBKhF - 27几乎完全抑制了从小脑平行纤维到浦肯野细胞的突触传递,而MK - 801具有同样强大的抗抑制作用,这主要证明了NMDA受体复合物的参与。