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(-)司来吉兰,一种作用于大脑的儿茶酚胺能活性增强剂(CAE)物质。

(-)Deprenyl (selegiline), a catecholaminergic activity enhancer (CAE) substance acting in the brain.

作者信息

Knoll J

机构信息

Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary.

出版信息

Pharmacol Toxicol. 1998 Feb;82(2):57-66. doi: 10.1111/j.1600-0773.1998.tb01399.x.

Abstract

beta-Phenylethylamine and its long acting derivatives, the amphetamines, are mixed-acting stimulants of the sympathetic system in the brain. They enhance the impulse propagation mediated release of catecholamines (catecholaminergic activity enhancer effect) and displace catecholamines from their stores (catecholamine releasing effect). (-)Deprenyl (selegiline), a close structural relative to (-)methamphetamine, is the first catecholaminergic activity enhancer substance in clinical use devoid of catecholamine releasing property, being therefore free of the 'cheese effect' and of the dependence capacity of the amphetamines. (-)Deprenyl is also a highly potent and selective, irreversible inhibitor of monoamine oxidase type B. (-)Deprenyl enhances superoxide dismutase and catalase activity in the striatum, protects the nigrostriatal dopaminergic neurons against selective neurotoxins (6-hydroxy-dopamine, MPTP, 4-N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine) and prevents characteristic age-related morphological changes in the neurocytes of the substantia nigra. Maintenance of rats on (-)deprenyl during the postdevelopmental phase of their life slows the age-related decline of sexual and learning performances and prolongs life significantly. Patients with early, untreated Parkinson's disease maintained on (-)deprenyl need levodopa significantly later than their placebo-treated peers, and when on levodopa plus (-)deprenyl, they live significantly longer than patients on levodopa alone. In patients with moderately severe impairment from Alzheimer's disease, treatment with (-)deprenyl slows the progression of the disease. It may be supposed that a prophylactic low dose administration of a safe catecholaminergic activity enhancer substance during the postdevelopmental phase of life will slow the age-related decline of behavioral performances, delay natural death and decrease susceptibility to Parkinson's disease and Alzheimer's disease.

摘要

β-苯乙胺及其长效衍生物苯丙胺类药物,是大脑交感神经系统的混合作用兴奋剂。它们能增强冲动传导介导的儿茶酚胺释放(儿茶酚胺能活性增强效应),并使儿茶酚胺从储存部位释放出来(儿茶酚胺释放效应)。(-)司来吉兰(Selegiline)是(-)甲基苯丙胺的结构类似物,是临床使用的第一种具有儿茶酚胺能活性增强特性且无儿茶酚胺释放特性的物质,因此没有“奶酪效应”以及苯丙胺类药物的成瘾性。(-)司来吉兰还是一种高效且选择性的不可逆单胺氧化酶B抑制剂。(-)司来吉兰可增强纹状体中超氧化物歧化酶和过氧化氢酶的活性,保护黑质纹状体多巴胺能神经元免受选择性神经毒素(6-羟基多巴胺、MPTP、4-N-(2-氯乙基)-N-乙基-2-溴苄胺)的损伤,并防止黑质神经细胞出现特征性的与年龄相关的形态变化。在大鼠发育后期给予(-)司来吉兰,可减缓与年龄相关的性功能和学习能力下降,并显著延长寿命。早期未治疗的帕金森病患者服用(-)司来吉兰后,比服用安慰剂的同龄人明显更晚需要左旋多巴治疗,并且在服用左旋多巴加(-)司来吉兰时,他们的寿命明显长于单独服用左旋多巴的患者。在患有中度严重阿尔茨海默病的患者中,用(-)司来吉兰治疗可减缓疾病进展。可以推测,在生命发育后期预防性低剂量给予安全的儿茶酚胺能活性增强物质,将减缓与年龄相关的行为能力下降,延迟自然死亡,并降低患帕金森病和阿尔茨海默病的易感性。

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