Lyles G A, Callingham B A
Biochem Pharmacol. 1982 Apr 1;31(7):1417-24. doi: 10.1016/0006-2952(82)90037-5.
Bernserazide (D,L-serine 2-[2,3,4-trihydroxybenzyl]-hydrazide) as been shown to inhibit the clorgyline-resistant amine oxidase (CRAO) activities which metabolize benzylamine in homogenates of rat aorta, heart and brown adipose tissue. In vitro studies showed a concentration- and time-dependent inhibition of CRAO in heart and aorta which was reversed by dialysis for 18hr. At high concentrations (10(-4)-10(-3)M) benserazide appeared to increase enzyme activity towards and occasionally above control value. These increases became more prominent after long periods of preincubation (especially in the presence of saturating benzylamine concentrations) and remained after dialysis of those homogenates preincubated with benserazide. The administration of benserazide for one or seven days in daily doses of 5-150 mg/kg also inhibited CRAO activity in vivo in a dose-dependent manner, with greater inhibition after seven days treatment. Reversal of inhibition, by dialysis of tissue homogenates from benserazide-treated rats, was much slower than was found with homogenates incubated in vitro with the drug. After benserazide administration to rats, MAO-A activity towards 5-hydroxytryptamine was generally not inhibited, and in fact was significantly increased in some cases. The administration of L-DOPA (250 mg/kg) together with benserazide (40 mg/kg) resulted in a similar degree of CRAO inhibition in aorta and heart to that seen after benserazide alone. These findings are discussed with regard to the use of these drugs in the therapy of Parkinson's Disease, although the paucity of information about the physiological function of CRAO makes the significance of its inhibition by benserazide unclear.
苄丝肼（D，L-丝氨酸2-[2,3,4-三羟基苄基]-酰肼）已被证明可抑制大鼠主动脉、心脏和棕色脂肪组织匀浆中代谢苄胺的氯吉兰抗性胺氧化酶（CRAO）活性。体外研究表明，苄丝肼对心脏和主动脉中的CRAO具有浓度和时间依赖性抑制作用，透析18小时后这种抑制作用可逆转。在高浓度（10⁻⁴ - 10⁻³M）下，苄丝肼似乎会增加酶活性，有时甚至高于对照值。长时间预孵育后（尤其是在苄胺浓度饱和的情况下），这些增加变得更加明显，并且在用苄丝肼预孵育的匀浆透析后仍然存在。以5 - 150 mg/kg的日剂量给予苄丝肼1天或7天，也会在体内以剂量依赖性方式抑制CRAO活性，7天治疗后的抑制作用更强。用透析法处理苄丝肼处理过的大鼠的组织匀浆来逆转抑制作用，比用药物在体外孵育匀浆时发现的情况要慢得多。给大鼠施用苄丝肼后，MAO - A对5 - 羟色胺的活性通常不受抑制，实际上在某些情况下还会显著增加。将L - DOPA（250 mg/kg）与苄丝肼（40 mg/kg）一起给药，在主动脉和心脏中产生的CRAO抑制程度与单独使用苄丝肼时相似。尽管关于CRAO生理功能的信息匮乏，使得苄丝肼对其抑制的意义尚不清楚，但还是就这些药物在帕金森病治疗中的应用对这些发现进行了讨论。
