BRAIN 2-PHENYLETHYLAMINE AS A MAJOR MEDIATOR FOR CENTRAL ACTIONS OF AMPHETAMINE AND METHYLPHENIDATE
BRAIN 2-PHENYLETHYLAMINE AS A MAJOR MEDIATOR FOR CENTRAL ACTIONS OF AMPHETAMINE AND METHYLPHENIDATE
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DOI：
10.1016/0024-3205(75)90147-2
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发表时间：
1975-01-01
期刊：
影响因子：
6.1
通讯作者：
SABELLI, HC
中科院分区：
文献类型：
--
作者：
BORISON, RL;MOSNAIM, AD;SABELLI, HC
用气-液色谱法测定了兔脑组织中2-苯乙胺(PEA)的含量。D-苯丙胺硫酸盐(0.65 mg/kg)最初将大脑PEA水平降低到其正常含量的三分之一(30分钟)，随后将大脑PEA增加一倍(4小时)。D-苯丙胺硫酸盐(13 mg/kg)降低了脑内PEA水平(30分钟)，随后又升高了10倍(4小时)；D-苯丙胺治疗3天后观察到对这两种影响的耐受性。盐酸哌甲酯(30 mg/kg)可引起脑组织PEA含量显著升高(4小时)，但对L-硫酸苯丙胺(0.65 mg/kg和13 mg/kg)无明显影响。D-苯丙胺(30min或4h前)可增加脑室注射标记苯丙氨酸后标记PEA的脑内回收率，降低脑室注射后标记PEA的回收率，提示D-苯丙胺可促进脑内PEA的合成和处置。用α-甲基多巴(可耗尽苯乙胺和其他脑胺)或α-甲基多巴肼(仅通过抑制外周组织中的脱羧酶来选择性地降低脑组织中苯乙醇胺的含量)可显著降低D-苯丙胺的中枢神经系统效应(对小鼠和兔的行为刺激，对小鼠的抗惊厥作用)；这些脱羧酶抑制剂增强了苯丙胺样作用。PEA选择性阻断D-苯丙胺的兴奋作用的能力减弱，再加上苯丙胺和PEA在结构和药理上的相似之处，以及苯丙胺对PEA脑水平、合成和代谢的显著影响，提示苯丙胺的许多中枢作用可能是由内源性PEA介导的。
2-Phenylethylamine (PEA) was measured in rabbit brain by gas-liquid chromatography. D-Amphetamine sulfate (0.65 mg/Kg) initially reduced brain PEA levels to one-third of its usual content (30 min) and subsequently doubled brain PEA (4 hr). Brain PEA levels were reduced (30 min) and subsequently increased (ten-fold at 4 hr) by D-amphetamine sulfate (13 mg/Kg); tolerance to these two effects was observed in rabbits treated for three days with D-amphetamine. Methylphenidate HCl (30 mg/Kg) but not L-amphetamine sulfate (0.65 mg/Kg and 13 mg/Kg) induced a small, non-significant lowering of brain PEA (30 min) followed by a marked augmentation (4 hr) of brain PEA content. D-Amphetamine (30 min or 4 hr prior) increased the recovery of labeled PEA from the brain of rabbits injected intraventricularly with labeled phenylalanine, and reduced the recovery of labeled PEA after its intraventricular injection, suggesting that D-amphetamine accelerates both the synthesis and the disposition of brain PEA. Pretreatment with α-methyldopa (which depletes PEA and other brain amines) or with α-methyldopa hydrazine (which selectively reduces brain PEA content by inhibiting decarboxylase in peripheral tissues only) markedly reduced the CNS effects of D-amphetamine (behavioral stimulation in mice and rabbits, anti-convulsant effect in mice); these decarboxylase inhibitors enhanced the amphetamine-like effects induced by PEA in mice pretreated with a monoamine oxidase inhibitor. The ability of PEA depleters to selectively block the stimulant effects of D-amphetamine, together with the close structural and pharmacological similarities between amphetamine and PEA, and marked influence of amphetamine administration upon PEA brain levels, synthesis and metabolism, suggest to us that many of the central actions of amphetamine may be mediated by endogenous PEA.