(-)Deprenyl and (-)1-phenyl-2-propylaminopentane, [(-)PPAP], act primarily as potent stimulants of action potential-transmitter release coupling in the catecholaminergic neurons.
(-)Deprenyl and (-)1-phenyl-2-propylaminopentane, [(-)PPAP], act primarily as potent stimulants of action potential-transmitter release coupling in the catecholaminergic neurons.
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(-)Deprenyl 和 (-)1-苯基-2-丙氨基戊烷 [(-)PPAP] 主要作为儿茶酚胺能神经元中动作电位-递质释放耦合的有效兴奋剂。
DOI：
10.1016/0024-3205(96)00014-8
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发表时间：
1996
期刊：
影响因子：
6.1
通讯作者：
K. Kelemen
中科院分区：
文献类型：
--
作者：
J. Knoll;I. Miklya;B. Knoll;R. Marko;K. Kelemen
在皮下注射非常小剂量的（-）Deprenyl（阈值剂量：去甲肾上腺素能神经元为0.01 mg/kg，多巴胺能神经元为0.025 mg/kg）后30分钟，大鼠脑中儿茶酚胺能神经元的活性显著增强。作为一种儿茶酚胺能活性增强剂（CAE）物质，（−）丙炔苯丙胺的效力比其母体化合物（−）甲基苯丙胺高出约10倍。虽然（+）甲基苯丙胺在释放儿茶酚胺方面比（-）甲基苯丙胺强3-5倍，但（-）甲基苯丙胺是更强的CAE物质。（-）丙炔苯丙胺和（-）PPAP（一种丙炔苯丙胺衍生物，无单胺氧化酶抑制作用）的CAE效应的机制，在大鼠中通过测定：a）纹状体、黑质、嗅结节和蓝斑的儿茶酚胺释放，B）刺激诱导的离体脑干的~ 3 H-去甲肾上腺素释放，以及（-）PPAP（一种丙炔苯丙胺衍生物，无单胺氧化酶抑制作用）的作用。和c）在穿梭箱中对丁苯那嗪诱导的学习抑郁的拮抗作用。发现CAE效应与以下因素无关：a）MAO活性的抑制; B）突触前儿茶酚胺受体的抑制; c）儿茶酚胺摄取的抑制;以及d）儿茶酚胺的释放。得出的结论是，（−）丙炔苯丙胺和（−）PPAP主要作为脑中儿茶酚胺能神经元的动作电位-递质释放偶联的强效兴奋剂。我们发现，（-）丙炔苯丙胺和（-）PPAP增强蛙心窦耳纤维的内向钙电流。在该试验中，（−）PPAP比（+）PPAP或（−）丙炔苯丙胺更有效。
The activity of the catecholaminergic neurons in the rat brain is enhanced significantly 30 min after the subcutaneous injection of very small doses of (−)deprenyl (threshold doses: 0.01 mg/kg for noradrenergic neurons and 0.025 mg/kg for dopaminergjc neurons). As a catecholaminergic activity enhancer (CAE) substance (−)deprenyl is about ten times more potent than its parent compound, (−)methamphetamine. While the (+)methamphetamine is 3–5 times more potent than (−)methamphetamine in releasing catecholamines, the (−)methamphetamine is the more potent CAE substance. The mechanism of the CAE effect of (−)deprenyl and (−)PPAP, a deprenyl-derived substance devoid of MAO inhibitory potency, was studied in rats by measuring: a) the release of catecholamines from striatum, substantia nigra, tuberculum olfactorium and locus coeruleus; b) the stimulation induced release of3H-noradrenaline from the isolated brain stem; and c) the antagonistic effect against tetrabenazine-induced depression of learning in the shuttle box. The CAE effect was found to be unrelated: a) to the inhibition of MAO activity; b) to the inhibition of presynaptic catecholamine receptors; c) to the inhibition of the uptake of catecholamines; and d) to the release of catecholamines. It was concluded that (−)deprenyl and (−)PPAP act primarily as potent stimulants of action potential-transmitter release coupling in the catecholaminergic neurons of the brain. We show that both (−)deprenyl and (−)PPAP enhance the inward Ca2+current in sino-auricular fibers of the frog heart. (−)PPAP was much more potent than either (+)PPAP or (−)deprenyl in this test.