盐酸瑞马西胺去甘氨酰代谢物（FPL 12495AA）和地佐环平（MK-801）对小鼠皮质内源性氨基酸释放的影响。

The effect of the desglycinyl metabolite of remacemide hydrochloride (FPL 12495AA) and dizocilpine (MK-801) on endogenous amino acid release from mouse cortex.

作者信息

Srinivasan J, Richens A, Davies J A

机构信息

Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Heath Park, Cardiff.

出版信息

Br J Pharmacol. 1995 Dec;116(8):3087-92. doi: 10.1111/j.1476-5381.1995.tb15109.x.

DOI:10.1111/j.1476-5381.1995.tb15109.x

PMID:8719781

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1909187/

Abstract

In this study the effect of FPL 12495AA, the desglycinyl metabolite of remacemide hydrochloride and dizocilpine (MK-801), on potassium- and veratridine-stimulated release of neurotransmitter amino acids from mouse cortical slices was investigated. 2. Veratridine (20 microM) and potassium (60 mM) produced a preferential release of glutamate and aspartate. Potassium-stimulated release was calcium-dependent, while veratridine-stimulated release was only partially affected by removal of calcium from the medium. 3. FPL 12495AA significantly inhibited veratridine- and potassium-stimulated release of glutamate and aspartate. Lower concentrations of FPL 12495AA were needed to inhibit veratridine-stimulated release of glutamate (12.5 microM) than potassium-stimulated release (100 microM). 4. Dizocilpine significantly inhibited veratridine- and potassium-stimulated release of glutamate and aspartate at concentrations of 100 microM and above. 5. FPL 12495AA and dizocilpine both have an affinity for the ion channel subsite of the N-methyl-D-aspartate (NMDA) receptor. The reduction of potassium-stimulated release of glutamate and aspartate by FPL 12495AA and dizocilpine is probably due to NMDA receptor blockade. 6. FPL 12495AA inhibited veratridine-stimulated release at a concentration of 12.5 microM while dizocilpine was effective only at a concentration of 100 microM. This difference in efficacy is probably due to the higher affinity of FPL 12495AA compared to dizocilpine at the veratridine-binding site on the sodium channel.

摘要

在本研究中，对盐酸瑞马西胺和地佐环平（MK-801）的去甘氨酰代谢物FPL 12495AA对小鼠皮质切片中钾离子和藜芦碱刺激的神经递质氨基酸释放的影响进行了研究。2. 藜芦碱（20微摩尔）和钾离子（60毫摩尔）优先促使谷氨酸和天冬氨酸释放。钾离子刺激的释放依赖于钙，而藜芦碱刺激的释放在从培养基中去除钙时仅受到部分影响。3. FPL 12495AA显著抑制藜芦碱和钾离子刺激的谷氨酸和天冬氨酸释放。抑制藜芦碱刺激的谷氨酸释放（12.5微摩尔）所需的FPL 12495AA浓度低于抑制钾离子刺激的释放（100微摩尔）所需的浓度。4. 地佐环平在100微摩尔及以上浓度时显著抑制藜芦碱和钾离子刺激的谷氨酸和天冬氨酸释放。5. FPL 12495AA和地佐环平均对N-甲基-D-天冬氨酸（NMDA）受体的离子通道亚位点具有亲和力。FPL 12495AA和地佐环平对钾离子刺激的谷氨酸和天冬氨酸释放的抑制作用可能是由于NMDA受体阻断。6. FPL 12495AA在12.5微摩尔浓度时抑制藜芦碱刺激的释放，而地佐环平仅在100微摩尔浓度时有效。这种效力差异可能是由于FPL 12495AA在地佐环平与钠通道上的藜芦碱结合位点相比具有更高的亲和力。