Beaton J M, Smythies J R, Bradley R J
Biol Psychiatry. 1975 Feb;10(1):45-52.
Several groups of investigators have reported that the administration of L-methionine, with or without a monoamine oxidase inhibitor, induced an acute florid psychotic reaction in 40 percent of schizophrenics tested. The mode of action of L-methionine in brain is unknown, but may be via one or more of three mechanisms: the excess methionine (i) may lead to the production by transmethylation of some psychotomimetic methylated derivative of dopamine or serotonin, or (ii) could result in an increase in the levels of a metabolite of methionine (e.g., homocysteine, cystathionine, or cysteine), or (iii) may effect the cellular uptake of other amino acids. In order to test the first two hypotheses, L-methionine, betaine (another metyl group donor), L-methionine plus L-serine, L-cysteine, L-serine, and saline (as a control) were studied on the sleep-wake cycles of random-bred Swiss mice and on the avoidance behavior or rats. L-methionine plus L-histidine, L-methionine plus nicotinamide, L-histidine, and nicotinamide were also tested in the mice. Daily injections of 250 mg/kg of these compounds were administered for at least 21 consecutive days. Schedule performance in the rat and the sleep-wake cycles of the mice were monitored during this period and compared to controls. L-Methionine induced behavioral and sleep cycle disturbances which were removed by the simultaneous administration of L-serine but not by the addition of L-histidine or nicotinamide. These data suggest that the disruption may be due to an increase in the levels of one of the metabolities of methionine, homocysteine, rather than to an increase in the number of available methyl groups.
几组研究人员报告称，给予L-蛋氨酸（无论是否同时给予单胺氧化酶抑制剂），在40%接受测试的精神分裂症患者中诱发了急性明显的精神病性反应。L-蛋氨酸在大脑中的作用方式尚不清楚，但可能通过以下三种机制中的一种或多种：过量的蛋氨酸（i）可能通过转甲基作用导致多巴胺或5-羟色胺的某些拟精神病性甲基化衍生物的产生，或者（ii）可能导致蛋氨酸的一种代谢产物（如高半胱氨酸、胱硫醚或半胱氨酸）水平升高，或者（iii）可能影响其他氨基酸的细胞摄取。为了检验前两个假设，研究了L-蛋氨酸、甜菜碱（另一种甲基供体）、L-蛋氨酸加L-丝氨酸、L-半胱氨酸、L-丝氨酸和生理盐水（作为对照）对随机繁殖的瑞士小鼠睡眠-觉醒周期以及大鼠回避行为的影响。还在小鼠中测试了L-蛋氨酸加L-组氨酸、L-蛋氨酸加烟酰胺、L-组氨酸和烟酰胺。每天以250mg/kg的剂量注射这些化合物，连续至少注射21天。在此期间监测大鼠的程序行为表现和小鼠的睡眠-觉醒周期，并与对照组进行比较。L-蛋氨酸诱发了行为和睡眠周期紊乱，同时给予L-丝氨酸可消除这些紊乱，但添加L-组氨酸或烟酰胺则不能。这些数据表明，这种紊乱可能是由于蛋氨酸的一种代谢产物高半胱氨酸水平升高，而不是由于可用甲基数量的增加。
