Tekes K, Tóthfalusi L, Gaál J, Magyar K
Department of Pharmacodynamics, Semmelweis Medical School, Budapest, Hungary.
Pol J Pharmacol Pharm. 1988 Nov-Dec;40(6):653-8.
Complex pharmacological effect of l-deprenyl cannot be explained by its MAO-B inhibitory action only. In contrast to other parent MAO inhibitors (J-512, J-516, LK-63, U-1424) l-, and d-deprenyl inhibit the hypothalamic noradrenaline and striatal dopamine (DA) reuptake without influencing the uptake of serotonin, both in rat and in human brain. Long-term treatment 19 x 0.25 mg/kg or 0.5 mg/kg, sc with l-deprenyl elicits 37 +/- 2.8 and 43 +/- 3.2% inhibition, respectively, of DA reuptake capacity in the rat striatal cell-free homogenate. To compare the potencies of deprenyl isomers on DA and DOPAC levels of rat striatum drugs were given 0.25, 2 and 8 mg/kg ip and their effects measured 4 and 48 h after treatment. DA content was increased only by 8 mg/kg d-deprenyl 4 h after its injection, but DOPAC level was decreased by both isomers. After 48 h, actions of d-deprenyl terminated but the effect of l-deprenyl was still present.
左旋司来吉兰的复杂药理作用不能仅用其对单胺氧化酶B(MAO-B)的抑制作用来解释。与其他母体单胺氧化酶抑制剂(J-512、J-516、LK-63、U-1424)不同,左旋和右旋司来吉兰在大鼠和人脑中均能抑制下丘脑去甲肾上腺素和纹状体多巴胺(DA)的再摄取,而不影响5-羟色胺的摄取。长期皮下注射19次,每次0.25mg/kg或0.5mg/kg的左旋司来吉兰,分别使大鼠纹状体无细胞匀浆中DA的再摄取能力受到37±2.8%和43±3.2%的抑制。为比较司来吉兰异构体对大鼠纹状体中DA和3,4-二羟基苯乙酸(DOPAC)水平的作用强度,腹腔注射给予0.25、2和8mg/kg的药物,并在给药后4小时和48小时测量其作用效果。注射后4小时,仅8mg/kg的右旋司来吉兰使DA含量增加,但两种异构体均使DOPAC水平降低。48小时后,右旋司来吉兰的作用消失,但左旋司来吉兰的作用仍然存在。