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芬氟拉明异构体和代谢物的厌食作用：脑内水平与对血清素能机制的体外效力之间的关系。

Anorectic effect of fenfluramine isomers and metabolites: relationship between brain levels and in vitro potencies on serotonergic mechanisms.

作者信息

Mennini T, Garattini S, Caccia S

出版信息

Psychopharmacology (Berl). 1985;85(1):111-4. doi: 10.1007/BF00427333.

DOI:10.1007/BF00427333
PMID:2984709
Abstract

A study of the possible molecular mechanisms of action by which the isomers and metabolites of fenfluramine increase serotonin transmission, leading to anorectic activity, is presented. The actual brain levels of fenfluramine and norfenfluramine isomers after administration of equi-anorectic doses to rats are compared with their potencies in affecting serotonergic mechanisms in vitro. Isomers and metabolites of fenfluramine can have the same pharmacological action by influencing serotonin uptake, release and binding in a quantitatively different manner.

摘要

本文介绍了一项关于芬氟拉明的异构体和代谢产物增加5-羟色胺传递从而导致厌食活性的可能分子作用机制的研究。将给大鼠服用等效厌食剂量后芬氟拉明和去甲芬氟拉明异构体的实际脑内水平与其在体外影响5-羟色胺能机制的效力进行了比较。芬氟拉明的异构体和代谢产物可通过以数量上不同的方式影响5-羟色胺的摄取、释放和结合而具有相同的药理作用。

相似文献

1
Anorectic effect of fenfluramine isomers and metabolites: relationship between brain levels and in vitro potencies on serotonergic mechanisms.芬氟拉明异构体和代谢物的厌食作用：脑内水平与对血清素能机制的体外效力之间的关系。
Psychopharmacology (Berl). 1985;85(1):111-4. doi: 10.1007/BF00427333.
2
Comparative studies on the anorectic activity of d-fenfluramine in mice, rats, and guinea pigs.右旋芬氟拉明对小鼠、大鼠和豚鼠厌食活性的比较研究。
Naunyn Schmiedebergs Arch Pharmacol. 1991 May;343(5):483-90. doi: 10.1007/BF00169550.
3
Fenfluramine and 5-hydroxytryptamine. Part 2: Involvement of brain 5-hydroxytryptamine in the anorectic activity of fenfluramine.芬氟拉明与5-羟色胺。第2部分：脑5-羟色胺在芬氟拉明厌食活性中的作用。
Arzneimittelforschung. 1975 Nov;25(11):1758-62.
4
Progress report on the anorectic effects of dexfenfluramine, fluoxetine and sertraline.
Int J Obes Relat Metab Disord. 1992 Dec;16 Suppl 3:S43-50.
5
d-Fenfluramine and salbutamol: two drugs causing anorexia through different neurochemical mechanisms.右旋芬氟拉明和沙丁胺醇：两种通过不同神经化学机制导致厌食的药物。
Int J Obes. 1984;8 Suppl 1:151-7.
6
Dissociation of the anorectic actions of 5-HTP and fenfluramine.5-羟色氨酸与芬氟拉明的食欲抑制作用的解离。
Psychopharmacology (Berl). 1986;89(2):216-20. doi: 10.1007/BF00310632.
7
Progress report on the anorexia induced by drugs believed to mimic some of the effects of serotonin on the central nervous system.
Am J Clin Nutr. 1992 Jan;55(1 Suppl):160S-166S. doi: 10.1093/ajcn/55.1.160s.
8
Different effects of fenfluramine isomers and metabolites on extracellular 5-HIAA in nucleus accumbens and hippocampus of freely moving rats.芬氟拉明异构体和代谢产物对自由活动大鼠伏隔核和海马细胞外5-羟吲哚乙酸的不同影响。
Eur J Pharmacol. 1988 Aug 24;153(2-3):295-9. doi: 10.1016/0014-2999(88)90618-8.
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Anorectic effect and brain concentrations of D-fenfluramine in the marmoset: relationship to the in vivo and in vitro effects on serotonergic mechanisms.
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Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications.5-羟色胺（2B）受体可能参与与芬氟拉明及其他血清素能药物相关的心脏瓣膜病的证据。
Circulation. 2000 Dec 5;102(23):2836-41. doi: 10.1161/01.cir.102.23.2836.

引用本文的文献

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Stereoselective Analysis of the Antiseizure Activity of Fenfluramine and Norfenfluramine in Mice: Is -Norfenfluramine a Better Follow-Up Compound to Racemic-Fenfluramine?芬氟拉明和去甲芬氟拉明对小鼠抗癫痫活性的立体选择性分析：去甲芬氟拉明是否是外消旋芬氟拉明更好的后续化合物？
Int J Mol Sci. 2024 Feb 21;25(5):2522. doi: 10.3390/ijms25052522.
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Investigating interactions between phentermine, dexfenfluramine, and 5-HT2C agonists, on food intake in the rat.研究苯丁胺、右芬氟拉明和5-羟色胺2C受体激动剂之间对大鼠食物摄入量的相互作用。
Psychopharmacology (Berl). 2015 Jun;232(11):1973-82. doi: 10.1007/s00213-014-3829-2. Epub 2014 Dec 20.
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本文引用的文献

1
Evidence of the existence of two different intraneuronal pools from which pharmacological agents can release serotonin.存在两种不同的神经元内池的证据，药理剂可从这些池释放5-羟色胺。
Neurochem Int. 1981;3(5):289-94. doi: 10.1016/0197-0186(81)90015-2.
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Kinetics of fenfluramine isomers in the rat.芬氟拉明异构体在大鼠体内的动力学
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Evidence that it is possible to cause anorexia by increasing release and/or directly stimulating postsynaptic serotonin receptors in the brain.
The lumped constant of α-methyl-l-tryptophan is not influenced by drugs acting through serotonergic system.
α-甲基-l-色氨酸的总常数不受作用于血清素能系统的药物影响。
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Serotonergic responses in depressed patients with or without a history of alcohol use disorders and healthy controls.有或无酒精使用障碍病史的抑郁症患者及健康对照者的5-羟色胺能反应。
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Labelled alpha-methyl-L-tryptophan as a tracer for the study of the brain serotonergic system.标记α-甲基-L-色氨酸作为研究脑血清素能系统的示踪剂。
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Acute and chronic D-fenfluramine treatments have different effects on serotonin synthesis rates in the rat brain: an autoradiographic study.急性和慢性右旋芬氟拉明治疗对大鼠大脑中血清素合成速率有不同影响：一项放射自显影研究。
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7
Behavioural evidence that d-fenfluramine-induced anorexia in the rat is not mediated by the 5-HT1A receptor subtype.行为学证据表明，右旋芬氟拉明在大鼠中诱导的厌食并非由5-HT1A受体亚型介导。
Psychopharmacology (Berl). 1996 May;125(2):168-75. doi: 10.1007/BF02249416.
8
In vitro and in vivo effects of the anorectic agent dexfenfluramine on the central serotoninergic neuronal systems of non-human primates. A comparison with the rat.
Naunyn Schmiedebergs Arch Pharmacol. 1996 May;353(6):641-7. doi: 10.1007/BF00167183.
9
Anorectic effect and brain concentrations of D-fenfluramine in the marmoset: relationship to the in vivo and in vitro effects on serotonergic mechanisms.
Naunyn Schmiedebergs Arch Pharmacol. 1993 Mar;347(3):306-12. doi: 10.1007/BF00167450.
10
Suppression of behavioral activity by norfenfluramine and related drugs in rats is not mediated by serotonin release.氟苯丙胺及相关药物对大鼠行为活动的抑制作用并非由血清素释放介导。
Psychopharmacology (Berl). 1993;111(2):169-78. doi: 10.1007/BF02245519.
有证据表明，通过增加大脑中血清素的释放和/或直接刺激突触后血清素受体有可能导致厌食症。
Prog Neuropsychopharmacol. 1980;4(4-5):363-9. doi: 10.1016/0364-7722(80)90006-5.
4
Changes in serotonin, but not catecholamine, receptor binding in the brain of morphine-dependent rats.吗啡依赖大鼠大脑中血清素而非儿茶酚胺受体结合的变化。
Mol Pharmacol. 1981 Sep;20(2):237-9.
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Differences between d-fenfluramine and d-norfenfluramine in serotonin presynaptic mechanisms.
J Neurochem. 1983 Mar;40(3):891-3. doi: 10.1111/j.1471-4159.1983.tb08065.x.
6
D-Fenfluramine and D-norfenfluramine reduce food intake by acting on different serotonin mechanisms in the rat brain.右旋芬氟拉明和去甲右旋芬氟拉明通过作用于大鼠大脑中不同的5-羟色胺机制来减少食物摄入量。
Pharmacol Res Commun. 1982 Jul;14(7):671-8. doi: 10.1016/s0031-6989(82)80025-8.
7
Is receptor activation involved in the mechanism by which (+)-fenfluramine and (+)-norfenfluramine deplete 5-hydroxytryptamine in the rat brain?（+）-芬氟拉明和（+）-去甲芬氟拉明使大鼠脑内5-羟色胺耗竭的机制涉及受体激活吗？
Br J Pharmacol. 1982 Mar;75(3):525-30. doi: 10.1111/j.1476-5381.1982.tb09169.x.
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Localization of fenfluramine and reserpine in brain regions of rats with extensive degeneration of 5-hydroxytryptaminergic neurons.
J Pharm Pharmacol. 1980 Jul;32(7):505-7. doi: 10.1111/j.2042-7158.1980.tb12980.x.
9
Gas-liquid chromatographic determination of the optical isomers of fenfluramine and norfenfluramine in biological samples.气相色谱法测定生物样品中芬氟拉明和去甲芬氟拉明的光学异构体
J Chromatogr. 1977 Nov 21;144(1):127-31. doi: 10.1016/0021-9673(77)80016-2.
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Stereoselective disposition of fenfluramine enantiomers in the rat.氟苯丙胺对映体在大鼠体内的立体选择性分布。
Xenobiotica. 1978 Sep;8(9):583-8. doi: 10.3109/00498257809061258.