Barroso N, Rodriguez M
Department of Physiology, Faculty of Medicine, University of La Laguna, Tenerife, Canary Islands, Spain.
Eur J Pharmacol. 1996 Feb 22;297(3):195-203. doi: 10.1016/0014-2999(95)00757-1.
The present paper describes the effect of beta-phenylethylamine and its metabolites phenylethanolamine, tyramine, acetyl-phenylethylamine and phenylacetaldehyde on the dopaminergic nigrostriatal system. The rotational behavioural response to the i.v. injection of these drugs was quantified in animals with a unilateral 6-hydroxydopamine lesion of the nigrostriatal dopamine system. Only beta-phenylethylamine and acetyl-phenylethylamine induced rotations ipsilateral to the side of the brain lesion. None of the compounds under study stimulated contralateral rotations. Acetyl-phenylethylamine was 90% less active than beta-phenylethylamine. After beta-phenylethylamine injection all animals (16/16) showed ipsilateral rotations. The dose-response curve showed that at doses as low as 1.75 mg/kg ipsilateral turns increase, with a dose-related rotational response between 1.75 mg/kg and 11.66 mg/kg, no differences being found at doses between 11.66 and 29.16 mg/kg. Rotations began a few seconds after beta-phenylethylamine injection. The highest response was found 30-60 s after the injection. The duration of the response was dose-related (4 min for the 3.5 mg/kg doses). The inhibition of dopamine-beta-hydroxylase activity with [1-3,5-difluorobenzyl)imidazole-2-thiol (SKF102698) did not modify the rotational response to beta-phenylethylamine. The inhibition of type B monoamine oxidase activity with l-deprenyl induced a slight increase in the ipsilateral rotational response to beta-phenylethylamine. The inhibition of tyrosine hydroxylase activity with alpha-methyl-p-tyrosine decreased the rotational response to beta-phenylethylamine. The dopamine receptor antagonist, haloperidol, completely blocked the ipsilateral rotational response to beta-phenylethylamine. The blocking of dopamine uptake into storage vesicles with reserpine increased the rotational action of beta-phenylethylamine. Taken together, the data suggest that, at low doses, beta-phenylethylamine stimulates the release of dopamine from the cytoplasmic pool and behaves as a dopamine receptor agonist with a very rapid and brief action.
本文描述了β-苯乙胺及其代谢产物苯乙醇胺、酪胺、乙酰-β-苯乙胺和苯乙醛对多巴胺能黑质纹状体系统的影响。在患有黑质纹状体多巴胺系统单侧6-羟基多巴胺损伤的动物中，对静脉注射这些药物后的旋转行为反应进行了量化。只有β-苯乙胺和乙酰-β-苯乙胺诱导了与脑损伤侧同侧的旋转。所研究的化合物均未刺激对侧旋转。乙酰-β-苯乙胺的活性比β-苯乙胺低90%。注射β-苯乙胺后，所有动物（16/16）均出现同侧旋转。剂量反应曲线表明，低至1.75mg/kg的剂量时同侧旋转增加，在1.75mg/kg至11.66mg/kg之间存在剂量相关的旋转反应，在11.66mg/kg至29.16mg/kg之间的剂量未发现差异。旋转在注射β-苯乙胺后几秒钟开始。注射后30-60秒发现最高反应。反应持续时间与剂量相关（3.5mg/kg剂量为4分钟）。用[1-（3,5-二氟苄基）咪唑-2-硫醇]（SKF102698）抑制多巴胺-β-羟化酶活性并未改变对β-苯乙胺的旋转反应。用l-司来吉兰抑制B型单胺氧化酶活性导致对β-苯乙胺的同侧旋转反应略有增加。用α-甲基-p-酪氨酸抑制酪氨酸羟化酶活性降低了对β-苯乙胺的旋转反应。多巴胺受体拮抗剂氟哌啶醇完全阻断了对β-苯乙胺的同侧旋转反应。用利血平阻断多巴胺摄取到储存囊泡中增加了β-苯乙胺的旋转作用。综上所述，数据表明，在低剂量下，β-苯乙胺刺激多巴胺从细胞质池中释放，并表现为一种作用非常迅速且短暂的多巴胺受体激动剂。
