LONG‐TERM EFFECTS OF N‐2‐CHLOROETHYL‐N‐ETHYL‐2‐BROMOBENZYLAMINE HYDROCHLORIDE ON NORADRENERGIC NEURONES IN THE RAT BRAIN AND HEART
LONG‐TERM EFFECTS OF N‐2‐CHLOROETHYL‐N‐ETHYL‐2‐BROMOBENZYLAMINE HYDROCHLORIDE ON NORADRENERGIC NEURONES IN THE RAT BRAIN AND HEART
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N-2-氯乙基-N-乙基-2-溴苄胺盐酸盐对大鼠脑和心脏去甲肾上腺素能神经元的长期影响
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发表时间：
1976
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通讯作者：
S. Ross
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作者：
S. Ross
1 N‐2‐氯乙基‐N‐乙基‐2‐溴苄胺盐化物（DSP 4） 50 mg/kg腹腔注射后8个月，脑浆液积累去甲肾上腺素的能力长期下降，效果显著。它对纹状体（多巴胺神经元）匀浆中去甲肾上腺素的摄取和各脑区5 -羟色胺（5 - HT）的摄取没有影响。2 .在体外实验中，DSP 4抑制皮质匀浆中去甲肾上腺素的摄取，IC50值为2 μm，但对纹状体匀浆中多巴胺摄取和皮质匀浆中5‐HT摄取的活性降低了10倍以上。3 . DSP 4 （50 mg/kg i.p）在体外抑制大鼠心房对去甲肾上腺素的摄取，但这种作用在2周内终止。dsp4 （50 mg/kg i.p.）引起大鼠大脑和心脏多巴胺- β -羟化酶（DBH）活性降低。这种效应的开始是缓慢的；心脏有2 ~ 4天的迟滞期。在大脑中，大脑皮层的DBH活性明显低于下丘脑，下丘脑仅受轻微影响。注射后8个月仍有显著效果。大脑中的去甲肾上腺素浓度大幅下降至少两周，而心脏中的去甲肾上腺素只是暂时下降。5 .地西帕明（10 mg/kg i.p）可拮抗DSP 4对大鼠脑内去甲肾上腺素积累、DBH活性和去甲肾上腺素浓度的长期影响。这表明DSP 4主要攻击膜上的去甲肾上腺素摄取位点，形成共价键，神经末梢由于这种结合而退化。
1 N‐2‐Chloroethyl‐N‐ethyl‐2‐bromobenzylamine hydrochloride (DSP 4) 50 mg/kg intraperitoneally, produced a long‐term decrease in the capacity of brain homogenates to accumulate noradrenaline with significant effect 8 months after the injection. It had no effect on the noradrenaline uptake in homogenates from the striatum (dopamine neurones) and on the uptake of 5‐hydroxytryptamine (5‐HT) in various brain regions. 2 In vitro DSP 4 inhibited the noradrenaline uptake in a cortical homogenate with an IC50 value of 2 μm but was more than ten times less active on the dopamine uptake in a striatal homogenate and the 5‐HT uptake in a cortical homogenate. 3 DSP 4 (50 mg/kg i.p.) inhibited the uptake of noradrenaline in the rat heart atrium in vitro but this action was terminated within 2 weeks. 4 DSP 4 (50 mg/kg i.p.) caused a decrease in the dopamine‐β‐hydroxylase (DBH) activity in the rat brain and heart. The onset of this effect was slow; in heart a lag period of 2–4 days was noted. In brain the DBH‐activity in cerebral cortex was much more decreased than that in hypothalamus which was only slightly affected. A significant effect was still found 8 months after the injection. The noradrenaline concentration in the brain was greatly decreased for at least two weeks, whereas noradrenaline in heart was only temporarily reduced. 5 The long‐term effects of DSP 4 on the noradrenaline accumulation, the DBH activity and noradrenaline concentration in the rat brain were antagonized by desipramine (10 mg/kg i.p.). 6 It is suggested that DSP 4 primarily attacks the membranal noradrenaline uptake sites forming a covalent bond and that the nerve terminals, as a result of this binding, degenerate.