Przewlocka B, Dziedzicka M, Silberring J, Lason W
Neuropeptides. 1986 Nov-Dec;8(4):359-65. doi: 10.1016/0143-4179(86)90007-7.
We studied behavioral effects of the intraventricularly and intrathecally administered guanidinoethylmercaptosuccinic acid (GEMSA) - a potent inhibitor of enkephalin convertase. When given intraventricularly in doses of 3 and 6 micrograms, GEMSA elicited analgesia; after doses of 12.5 and 25 micrograms the explosive motor behavior and convulsions occurred. Following the intrathecal administration of GEMSA (12.5, 25 and 50 micrograms), an increase in the tail-flick latency was observed; moreover that drug potentiated analgesic effects of the intrathecally applied Met5-enkephalin-Arg6-Phe7 and Met5-enkephalin-Arg6-Gly7-Leu8. All the above effects of GEMSA were significantly attenuated by naloxone. The rats subjected to chronic pain showed a weaker analgesic response to the intrathecally injected GEMSA. The 3H-GEMSA binding to enkephalin convertase in the spinal cord of these rats produced only a slight increase in KD; besides, no changes in the enzyme activity were observed. The study shows that GEMSA has a potent pharmacological action in the central nervous system. Furthermore, this effect is partly due to the influence of GEMSA on endogenous opioid peptide systems, possibly on proenkephalin A.
我们研究了脑室内和鞘内注射胍基乙硫基琥珀酸（GEMSA）——一种脑啡肽转换酶的强效抑制剂——的行为学效应。当以3微克和6微克的剂量脑室内给药时，GEMSA引发镇痛作用；在12.5微克和25微克的剂量后，出现爆发性运动行为和惊厥。鞘内注射GEMSA（12.5微克、25微克和50微克）后，观察到甩尾潜伏期延长；此外，该药物增强了鞘内应用的甲硫氨酸脑啡肽-精氨酸6-苯丙氨酸7和甲硫氨酸脑啡肽-精氨酸6-甘氨酸7-亮氨酸8的镇痛作用。GEMSA的所有上述效应均被纳洛酮显著减弱。遭受慢性疼痛的大鼠对鞘内注射的GEMSA的镇痛反应较弱。在这些大鼠的脊髓中，3H-GEMSA与脑啡肽转换酶的结合仅使解离常数（KD）略有增加；此外，未观察到酶活性的变化。该研究表明，GEMSA在中枢神经系统中具有强效的药理作用。此外，这种效应部分归因于GEMSA对内源性阿片肽系统的影响，可能是对前脑啡肽A的影响。
