Widerlöv E, Lewander T
Naunyn Schmiedebergs Arch Pharmacol. 1978 Sep;304(2):125-34. doi: 10.1007/BF00495548.
The time-course and the dose-response relationship for the antagonistic effect of alpha-methyl-p-tyrosine methyl ester HCl H 44/68 (alpha-MT) on d-amphetamine (10.6 mumoles/kg) induced increase in motor activity was studied. The effect of amphetamine was gradually reduced from 30--60 min to a minimum at 1--4 h after the administration of 0.407 mmoles/kg of alpha-MT. From (4--) 8 h the amphetamine response started to reappear and the original response was restored completely at 16 h after alpha-MT. The dose-response curve showed, that between 0.051--0.41 mmoles/kg of alpha-MT, given 1 h before amphetamine, there was a gradual reduction of the amphetamine response; doses above 0.41 mmoles/kg did not cause any further effect. The antiamphetamine action of alpha-MT was compared with its time- and dose-dependent effects of inhibition of synthesis and reduction of stores of brain catecholamines. It was found, that the antiamphetamine action was more closely correlated with the reduction of the levels of brain dopamine, than with the brain noradrenaline levels. Further, the inhibition of catecholamine synthesis per se did not appear to be a sufficient condition for alpha-MT induced antagonism of amphetamine. These findings support the view that amphetamine is dependent on a substantial portion of the brain pool of dopamine and possibly noradrenaline rather than on very small, newly synthesized pools of these neurotransmitters.
研究了盐酸α-甲基-对-酪氨酸甲酯H 44/68（α-MT）对d-苯丙胺（10.6微摩尔/千克）诱导的运动活动增加的拮抗作用的时程和剂量反应关系。在给予0.407毫摩尔/千克的α-MT后，苯丙胺的作用在30 - 60分钟逐渐减弱，在1 - 4小时降至最低。从（4 - ）8小时起，苯丙胺反应开始重新出现，在给予α-MT后16小时原始反应完全恢复。剂量反应曲线表明，在苯丙胺给药前1小时给予0.051 - 0.41毫摩尔/千克的α-MT时，苯丙胺反应逐渐减弱；高于0.41毫摩尔/千克的剂量没有产生进一步的影响。将α-MT的抗苯丙胺作用与其抑制脑儿茶酚胺合成和减少其储存的时间和剂量依赖性效应进行了比较。发现抗苯丙胺作用与脑多巴胺水平的降低比与脑去甲肾上腺素水平的降低更密切相关。此外，儿茶酚胺合成的抑制本身似乎不是α-MT诱导的苯丙胺拮抗作用的充分条件。这些发现支持这样一种观点，即苯丙胺依赖于脑中相当一部分多巴胺池，可能还有去甲肾上腺素池，而不是这些神经递质的非常小的新合成池。
