Hergovich N, Singer E, Agneter E, Eichler H G, Graselli U, Simhandl C, Jilma B
Department of Clinical Pharmacology, Vienna University School of Medicine, Vienna, Austria.
Neuropsychopharmacology. 2001 May;24(5):590-3. doi: 10.1016/S0893-133X(00)00194-9.
N-methyl D-aspartate (NMDA)-antagonists decrease neurotoxicity by inhibiting Ca2+ influx which is of interest for the treatment of acute cerebrovascular insults and chronic neurodegenerative disorders. Currently, there is no surrogate marker for quantification of NMDA-receptor-mediated drug effects, which hampers dose-finding clinical studies. As prolactin and cortisol liberation is in part influenced through NMDA-receptors we investigated whether the elevation of prolactin or cortisol plasma levels is a class effect of NMDA-antagonists and might be an appropriate marker for studying NMDA-antagonistic potency. Fifteen healthy male volunteers participated in this placebo-controlled, randomized, three-way crossover trial. Ketamine (0.5mg/kg), memantine (0.16 mg/kg; i.e., a well tolerated standard dose) or placebo were infused over 60 min. Ketamine increased serum prolactin and cortisol levels (p < 0.001), whereas memantine and placebo did not affect hormone levels. Further studies are needed to define whether higher doses of memantine or other NMDA antagonists can induce hormone release.
N-甲基-D-天冬氨酸（NMDA）拮抗剂通过抑制钙离子内流来降低神经毒性，这对于急性脑血管损伤和慢性神经退行性疾病的治疗具有重要意义。目前，尚无用于量化NMDA受体介导的药物效应的替代标志物，这阻碍了剂量探索性临床研究。由于催乳素和皮质醇的释放部分受NMDA受体影响，我们研究了血浆催乳素或皮质醇水平的升高是否是NMDA拮抗剂的类效应，以及是否可能是研究NMDA拮抗效力的合适标志物。15名健康男性志愿者参与了这项安慰剂对照、随机、三交叉试验。氯胺酮（0.5mg/kg）、美金刚（0.16mg/kg，即一个耐受性良好的标准剂量）或安慰剂经60分钟静脉输注。氯胺酮可提高血清催乳素和皮质醇水平（p<0.001），而美金刚和安慰剂对激素水平无影响。需要进一步研究来确定更高剂量的美金刚或其他NMDA拮抗剂是否能诱导激素释放。
