BENZOQUINOLIZINE DERIVATIVES - A NEW CLASS OF MONAMINE DECREASING DRUGS WITH PSYCHOTROPIC ACTION
BENZOQUINOLIZINE DERIVATIVES - A NEW CLASS OF MONAMINE DECREASING DRUGS WITH PSYCHOTROPIC ACTION
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DOI：
10.1016/s0074-7742(08)60024-0
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发表时间：
1962-01-01
影响因子：
--
通讯作者：
GEY, KF
中科院分区：
文献类型：
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作者：
PLETSCHER, A;BROSSI, A;GEY, KF
化学成分：在1，2，3，4，6，7-六氢-11bH-苯并[a]喹嗪衍生物中，酮（IVb）、仲醇（Va）和叔醇（VIa和VIb）显示出最有趣的生物学性质。药物代谢：丁苯那嗪的生物半衰期为几小时，根据器官和动物物种而有所不同。这种药对人体脂肪有特殊的亲和力。已鉴别出两种代谢物。对单胺代谢的影响：几种苯并喹嗪类药物，例如，丁苯那嗪、Ro 4-1284、Ro 4-1632、Ro 4-1860和Ro 4-1286优先降低脑中的5-羟色胺和儿茶酚胺含量。与利血平相比，它们的效力较低，但持续时间较短，起效较快。单胺抑制可通过单胺氧化酶抑制剂预处理来抵消。在脑内，丁苯那嗪阻止利血平引起的5-羟色胺的减少，但不能阻止去甲肾上腺素的减少。此外，丁苯那嗪增加尿液中的5-羟基吲哚乙酸。苯并喹嗪类药物对单胺代谢的影响可能是由于单胺在组织中的储存受损。药理学：单胺抑制剂苯并喹嗪影响中枢和自主神经系统，例如，它们诱导镇静、麻醉增强、低温、戊四唑惊厥的增强、条件反射的减少和副交感神经紧张的流行。这些行动平行的抑郁症的大脑单胺和持续时间短于利血平。单胺氧化酶抑制剂可以拮抗或逆转其中的几种作用。丁苯那嗪防止利血平诱导的镇静作用。一些苯并喹嗪衍生物引起中度低血压，可能是通过与脑和心脏中的单胺抑制无关的中枢和外周机制。苯并喹嗪对胃肠道功能的影响不如利血平明显。临床效果：丁苯那嗪具有镇静作用，对精神分裂症的各种症状以及亨廷顿舞蹈病具有有益作用。用苯并喹嗪获得的结果支持这样的假设，即对中枢神经系统的某些作用，如镇静作用，可能是通过大脑单胺的变化介导的。86篇参考文献。
Chemistry: Among the derivatives of 1,2,3,4,6,7-hexahydro-11bH-benzo[a]quinolizines the ketones (IVb), the secondary carbinols (Va), and the tertiary carbinols (VIa and VIb) show the most interesting biological properties. Drug metabolism: Tetrabenazine has a biological half-life of a few hours, varying according to the organ and the animal species. The drug shows a special affinity for body fat. Two metabolites have been identified. Effect on Monamine Metabolism: Several benzoquinolizines, e.g., tetrabenazine, Ro 4-1284, Ro 4-1632, Ro 4-1860, and Ro 4-1286, decrease the 5-hydroxytryptamine and catechol amine contents preferentially in the brain. Compared to reserpine they are less potent but of shorter duration and faster onset of action. The monamine depression is counteracted by pretreatment with monamine oxidase inhibitors. In brain, tetrabenazine prevents the reserpine-induced decrease of 5-hydroxytryptamine, but not that of norepinephrine. In addition, tetrabenazine increases 5-hydroxyindolylacetic acid in the urine. The effect of benzoquinolizines on monamine metabolism is probably due to an impairment of monamine storing in the tissue. Pharmacology: Monamine-depressing benzoquinolizines influence the central and the autonomic nervous system, e.g., they induce sedation, narcosis potentiation, hypothermia, enhancement of pentylenetetrazole convulsions, decrease of conditioned reflexes, and prevalence of parasympathetic nerve tone. These actions parallel the depression of cerebral monamines and are of shorter duration than those of reserpine. Monamine oxidase inhibitors antagonize or reverse several of these effects. Tetrabenazine prevents the reserpine-induced sedation. Some benzoquinolizine derivatives cause moderate hypotension, probably by central and peripheral mechanisms unrelated to monamine depression in brain and heart The effects of benzoquinolizines on gastrointestinal functions are less pronounced than with reserpine. Clinical effects: Tetrabenazine exerts a sedative action and has beneficial effects on various symptoms of schizophrenia as well as in Huntington''s chorea. The results obtained with the benzoquinolizine support the hypothesis that certain effects on the central nervous system, like sedation, might be mediated through changes in cerebral monamines. 86 references.