三环类抗抑郁药对大鼠脑匀浆中5-羟色胺能神经元突触体摄取5-羟色胺的抑制作用的构效关系。
Structure-activity relations for the inhibition of 5-hydroxytryptamine uptake by tricyclic antidepressants into synaptosomes from serotoninergic neurones in rat brain homogenates.
作者信息
Horn A S, Trace R C
出版信息
Br J Pharmacol. 1974 Jul;51(3):399-403. doi: 10.1111/j.1476-5381.1974.tb10675.x.
Abstract
1 The inhibitory effects of various analogues of imipramine on [(3)H]-5-hydroxytryptamine (5-HT) uptake into homogenates of rat hypothalamus were examined.2 For structures with a three carbon side chain the tertiary amine derivative was more potent than the compound with a secondary amine function.3 Potency was reduced by increasing or decreasing the length of the three carbon side chain by one carbon atom.4 Substitution of a methyl group in the alpha or beta position in the side chain reduced potency.5 Replacement of the dimethylene bridge in imipramine by a sulphur atom or substitution of a C=C double bond for the exocyclic N-C bond of imipramine both led to a fall in potency.6 3-Chlorimipramine was the most potent inhibitor of [(3)H]-5-hydroxytryptamine uptake of the compounds tested.
摘要
研究了丙咪嗪各种类似物对[(3)H]-5-羟色胺（5-HT）摄取到大鼠下丘脑匀浆中的抑制作用。
对于具有三个碳侧链的结构，叔胺衍生物比具有仲胺官能团的化合物更有效。
通过将三个碳侧链的长度增加或减少一个碳原子，效力降低。
在侧链的α或β位取代甲基会降低效力。
用硫原子取代丙咪嗪中的二亚甲基桥或用碳碳双键取代丙咪嗪的环外氮碳键均导致效力下降。
在测试的化合物中，3-氯丙咪嗪是[(3)H]-5-羟色胺摄取的最有效抑制剂。
相似文献
1
Structure-activity relations for the inhibition of 5-hydroxytryptamine uptake by tricyclic antidepressants into synaptosomes from serotoninergic neurones in rat brain homogenates.三环类抗抑郁药对大鼠脑匀浆中5-羟色胺能神经元突触体摄取5-羟色胺的抑制作用的构效关系。
Br J Pharmacol. 1974 Jul;51(3):399-403. doi: 10.1111/j.1476-5381.1974.tb10675.x.
2
A new modification for studying 5-HT uptake by blood platelets: a re-evaluation of tricyclic antidepressants as uptake inhibitors.一种研究血小板对5-羟色胺摄取的新改良方法：三环类抗抑郁药作为摄取抑制剂的重新评估。
J Pharm Pharmacol. 1974 Feb;26(2):92-100. doi: 10.1111/j.2042-7158.1974.tb09231.x.
3
Tricyclic antidepressant agents. I. Comparison of the inhibition of the uptake of 3-H-noradrenaline and 14-C-5-hydroxytryptamine in slices and crude synaptosome preparations of the midbrain-hypothalamus region of the rat brain.三环类抗抑郁药。I. 大鼠脑下丘脑-中脑区域切片和粗制突触体制剂中3-H-去甲肾上腺素和14-C-5-羟色胺摄取抑制作用的比较。
Acta Pharmacol Toxicol (Copenh). 1975;36(Suppl 5):382-94. doi: 10.1111/j.1600-0773.1975.tb00806.x.
4
Tricyclic antidepressant agents. II. Effect of oral administration on the uptake of 3-H-noradrenaline and 14-C-5-hydroxytryptamine in slices of the midbrain-hypothalamus region of the rat.三环类抗抑郁药。II. 口服给药对大鼠中脑-下丘脑区域切片中3-H-去甲肾上腺素和14-C-5-羟色胺摄取的影响。
Acta Pharmacol Toxicol (Copenh). 1975;36(Suppl 5):395-408. doi: 10.1111/j.1600-0773.1975.tb00807.x.
5
6
Regulation of high- and low-affinity [3H]imipramine recognition sites in rat brain by chronic treatment with antidepressants.抗抑郁药长期治疗对大鼠脑中高亲和力和低亲和力[³H]丙咪嗪识别位点的调节作用。
Eur J Pharmacol. 1987 Jun 19;138(2):159-68. doi: 10.1016/0014-2999(87)90429-8.
7
Inhibition of in vitro amine uptake into rat brain synaptosomes after in vivo administration of antidepressants.体内给予抗抑郁药后对大鼠脑突触体体外胺摄取的抑制作用。
Eur J Pharmacol. 1983 Nov 25;95(3-4):305-9. doi: 10.1016/0014-2999(83)90652-0.
8
Effect of a specific 5-HT uptake inhibitor, citalopram (Lu 10-171), on 3H-5-HT uptake in rat brain synaptosomes in vitro.一种特异性5-羟色胺摄取抑制剂西酞普兰（Lu 10-171）对大鼠脑突触体体外3H-5-羟色胺摄取的影响。
Psychopharmacology (Berl). 1978 Dec 15;60(1):13-8. doi: 10.1007/BF00429172.
9
Effects of mianserin, a new antidepressant, on the in vitro and in vivo uptake of monoamines.新型抗抑郁药米安色林对单胺类物质体外和体内摄取的影响。
Br J Pharmacol. 1977 Oct;61(2):307-13. doi: 10.1111/j.1476-5381.1977.tb08420.x.
10
Inhibition of (3H)-dopamine uptake into rat brain synaptosomes by the new non-tricyclic antidepressants, FS32 and FS97.新型非三环类抗抑郁药FS32和FS97对（3H）-多巴胺摄取到大鼠脑突触体的抑制作用。
Eur J Pharmacol. 1980 Mar 21;62(2-3):147-55. doi: 10.1016/0014-2999(80)90271-x.
引用本文的文献
1
Azidobupramine, an Antidepressant-Derived Bifunctional Neurotransmitter Transporter Ligand Allowing Covalent Labeling and Attachment of Fluorophores.叠氮布普品，一种源自抗抑郁药的双功能神经递质转运体配体，可实现荧光团的共价标记与连接。
PLoS One. 2016 Feb 10;11(2):e0148608. doi: 10.1371/journal.pone.0148608. eCollection 2016.
2
Binding and orientation of tricyclic antidepressants within the central substrate site of the human serotonin transporter.三环类抗抑郁药在人血清素转运体中枢基质部位的结合和取向。
J Biol Chem. 2010 Mar 12;285(11):8363-74. doi: 10.1074/jbc.M109.045401. Epub 2009 Nov 30.
3
Neuropharmacology of 5-hydroxytryptamine.5-羟色胺的神经药理学
Br J Pharmacol. 2006 Jan;147 Suppl 1(Suppl 1):S145-52. doi: 10.1038/sj.bjp.0706427.
4
Changes in histamine and serotonin secretion from rat peritoneal mast cells caused by antidepressants.抗抑郁药引起的大鼠腹膜肥大细胞组胺和5-羟色胺分泌的变化
Inflamm Res. 1996 Mar;45(3):141-4. doi: 10.1007/BF02265168.
5
Effect of chronic antidepressant treatment and subsequent withdrawal on [3H]-5-hydroxytryptamine and [3H]-spiperone binding in rat frontal cortex and serotonin receptor mediated behaviour.慢性抗抑郁药治疗及随后撤药对大鼠额叶皮质中[3H]-5-羟色胺和[3H]-螺哌隆结合以及5-羟色胺受体介导行为的影响。
Psychopharmacology (Berl). 1983;80(2):150-5. doi: 10.1007/BF00427959.
6
The activity of amitriptyline as a differential inhibitor of amine secretion from rat peritoneal mast cells: the contribution of amine uptake.阿米替林作为大鼠腹膜肥大细胞胺分泌差异抑制剂的活性：胺摄取的作用。
Agents Actions. 1990 Apr;30(1-2):41-3. doi: 10.1007/BF01968993.
7
Differential release of histamine and 5-hydroxytryptamine from rat mast cells: the contribution of amine uptake to the apparent pattern of secretion.大鼠肥大细胞中组胺和5-羟色胺的差异释放：胺摄取对明显分泌模式的作用。
Agents Actions. 1990 Apr;30(1-2):38-40. doi: 10.1007/BF01968992.
8
Effect of doxepin on uptake and efflux of serotonin human blood patelets in vitro.多塞平对人血血小板5-羟色胺摄取与外排的体外效应。
Psychopharmacologia. 1976 May 28;47(2):183-6. doi: 10.1007/BF00735819.
9
Effect of nomifensine on brain amines and epilepsy in photosensitive baboons.诺米芬辛对光敏狒狒脑胺及癫痫的影响。
Br J Clin Pharmacol. 1977;4Suppl 2(Suppl 2):101S-107S. doi: 10.1111/j.1365-2125.1977.tb05735.x.
10
Seizure activity in photosensitive baboons following antidepressant drugs and the role of serotoninergic mechanisms.抗抑郁药物作用下光敏狒狒的癫痫发作活动及5-羟色胺能机制的作用。
Psychopharmacology (Berl). 1977 Jan 31;51(2):159-64. doi: 10.1007/BF00431733.
本文引用的文献
1
Effect of antidepressant drugs on the depletion of intraneuronal brain 5-hydroxytryptamine stores caused by 4-methyl-alpha-ethyl-meta-tyramine.抗抑郁药物对4-甲基-α-乙基-间酪氨酸所致脑内神经元5-羟色胺储备耗竭的影响。
Eur J Pharmacol. 1969 Mar;5(4):357-66. doi: 10.1016/0014-2999(69)90113-7.
2
Regional differences in H3-norepinephrine and H3-dopamine uptake into rat brain homogenates.大鼠脑匀浆中H3-去甲肾上腺素和H3-多巴胺摄取的区域差异。
J Pharmacol Exp Ther. 1969 Jan;165(1):78-86.
3
4
5
Effect of desmethylimipramine, iprindole and DL-erythro-alpha-(3,4-dichlorophenyl)-beta-(t-butyl amino) propanol HC1 on the metabolism of amphetamine.去甲丙咪嗪、茚满二酮和盐酸 DL-赤藓醇-α-(3,4-二氯苯基)-β-(叔丁基氨基)丙醇对苯丙胺代谢的影响。
Biochem Pharmacol. 1970 Dec;19(12):3021-8. doi: 10.1016/0006-2952(70)90088-2.
6
Inhibition of the uptake of tritiated 5-hydroxytryptamine in brain tissue.脑组织中氚标记的5-羟色胺摄取的抑制作用。
Eur J Pharmacol. 1969 Sep;7(3):270-7. doi: 10.1016/0014-2999(69)90091-0.
7
Biogenic amines and emotion.生物胺与情绪。
Science. 1967 Apr 7;156(3771):21-37. doi: 10.1126/science.156.3771.21.
8
5-hydroxytryptamine uptake by rat brain in vitro.大鼠脑体外摄取5-羟色胺
Life Sci. 1967 Aug 1;6(15):1653-63. doi: 10.1016/0024-3205(67)90176-2.
9
The tricyclic antidepressants--inhibition of norepinephrine uptake as related to potentiation of norepinephrine and clinical efficacy.三环类抗抑郁药——去甲肾上腺素摄取抑制与去甲肾上腺素增强及临床疗效的关系。
Biochem Pharmacol. 1971 Feb;20(2):482-6. doi: 10.1016/0006-2952(71)90086-4.
10
A comparison of the inhibitory activities of iprindole and imipramine on the uptake of 5-hydroxytryptamine and noradrenaline in brain slices.茚满二氮卓和丙咪嗪对脑切片中5-羟色胺和去甲肾上腺素摄取抑制活性的比较。
Life Sci I. 1971 Nov 15;10(22):1267-77. doi: 10.1016/0024-3205(71)90325-0.
Zotero 插件