de Varebeke P J, Niebes P, Pauwels G, Roba J, Korf J
Biochem Pharmacol. 1983 Sep 15;32(18):2751-5. doi: 10.1016/0006-2952(83)90087-4.
Milacemide (CP 1552 S, 2-n-pentylaminoacetamide), a drug with anti-epileptic potency, increases the gamma-aminobutyric acid (GABA) content specifically in the substantia nigra of rat brain. The effect is dose-related from 25 to 100 mg/kg p.o. The time course shows that at 100 mg/kg p.o. after 2, 3 and 4 hr the substantia nigra GABA content is significantly increased by 28, 33 and 38%, respectively. After 6 hr the GABA contents return to the control value. After repeated oral administration of milacemide a comparable effect to acute administration is obtained. After degeneration of the striato-nigral GABA-ergic pathway, milacemide no longer enhances the content of GABA in the substantia nigra. GABA-transaminase activity measured ex vivo in rat brain homogenate is not influenced by milacemide. On the other hand, the glutamate decarboxylase activity measured ex vivo 3 hr after 100 mg/kg of milacemide is significantly increased by 11% in homogenates of the whole rat brain. The results show that milacemide increases the GABA content in the GABA pool which is associated with the striato-nigral neurons. This increase is not due to GABA-transaminase inhibition but might be the result of an enhanced synthesis, possibly through glutamate decarboxylase activation.
米拉美胺（CP 1552 S，2 - 正戊基氨基乙酰胺）是一种具有抗癫痫效力的药物，它能特异性地增加大鼠脑黑质中γ - 氨基丁酸（GABA）的含量。口服剂量在25至100 mg/kg时，该作用呈剂量相关性。时间进程显示，口服100 mg/kg后2、3和4小时，黑质中GABA含量分别显著增加28%、33%和38%。6小时后，GABA含量恢复到对照值。重复口服米拉美胺可获得与急性给药相当的效果。纹状体 - 黑质GABA能通路变性后，米拉美胺不再提高黑质中GABA的含量。在大鼠脑匀浆中离体测定的GABA转氨酶活性不受米拉美胺影响。另一方面，口服100 mg/kg米拉美胺3小时后，在整个大鼠脑匀浆中离体测定的谷氨酸脱羧酶活性显著增加11%。结果表明，米拉美胺增加了与纹状体 - 黑质神经元相关的GABA池中GABA的含量。这种增加并非由于GABA转氨酶抑制，而是可能通过谷氨酸脱羧酶激活导致合成增强的结果。
