Moncada C R, Arvin B, Meldrum B S
Department of Neurology, Institute of Psychiatry, London, UK.
Neurosci Lett. 1994 Sep 26;179(1-2):17-20. doi: 10.1016/0304-3940(94)90924-5.
We have investigated the neuroprotective effect of the pyrimidine derivative BW 1003C87 (5-[2,3,5-trichlorophenyl] pyrimidine-2,4-diamine ethane sulphonate) against striatal and hippocampal lesions induced by kainic acid (KA), N-methyl-D-aspartate (NMDA) and (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ((S)-AMPA) in the rat. BW 1003C87 20 mg/kg i.p. administered pre- and post-treatment (20 min prior to excitotoxic injection and again 4 h later) protects against the lesions induced by KA (1.1 nmol) in the hippocampus (CA2 pyramidal cells only; 40% protection, P < 0.05). In the striatum, the same dose of BW 1003C87 significantly reduces KA toxicity (80% protection, P < 0.001). BW 1003C87 has no significant effect on the lesions induced by NMDA (30 nmol) or S-AMPA (6 nmol) in either brain region. These results are consistent with previous studies showing that the neurotoxicity of KA occurs via an indirect mechanism involving glutamate release.
我们研究了嘧啶衍生物BW 1003C87（5-[2,3,5-三氯苯基]嘧啶-2,4-二胺乙烷磺酸盐）对大鼠中由 kainic 酸（KA）、N-甲基-D-天冬氨酸（NMDA）和（S）-α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（（S）-AMPA）诱导的纹状体和海马损伤的神经保护作用。BW 1003C87以20mg/kg腹腔注射，在治疗前和治疗后（兴奋性毒性注射前20分钟，4小时后再次注射）给药，可预防KA（1.1nmol）诱导的海马损伤（仅CA2锥体细胞；保护率40%，P<0.05）。在纹状体中，相同剂量的BW 1003C87可显著降低KA毒性（保护率80%，P<0.001）。BW 1003C87对NMDA（30nmol）或S-AMPA（6nmol）在两个脑区诱导的损伤均无显著影响。这些结果与先前的研究一致，表明KA的神经毒性通过涉及谷氨酸释放的间接机制发生。
