Highly potent neurotensin analog that causes hypothermia and antinociception
Highly potent neurotensin analog that causes hypothermia and antinociception
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DOI：
10.1016/s0014-2999(99)00877-8
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发表时间：
2000-02-25
影响因子：
5
通讯作者：
Richelson, E
中科院分区：
文献类型：
--
作者：
Tyler-McMahon, BM;Stewart, JA;Richelson, E
十三肽神经降压素长期以来被认为是一种内源性精神安定药。然而，为了使神经降压素[或神经降压素(8-13) [NT(8-13)]，活性片段]产生作用，必须集中给药。在此，我们报道了 NT(8-13), (N-methyl-Arg),Lys,Pro,L-neo-Trp, tert-Leu,Leu (NT69L) 的类似物，其含有一种新氨基酸 L-新色氨酸，对大鼠和人类神经降压素受体 1 亚型表现出高亲和力。腹膜内 (i.p.) 注射 (1 mg/kg) 后，NT69L 诱导> 5 摄氏度（直肠）的低温，显着效果持续超过 7 小时。根据热板试验的结果，NT69L 还引起快速（15 分钟内）和持久（超过 5 小时）的镇痛作用。总体而言，NT69L 是已报道的最有效、持续时间最长的神经降压素类似物。这些研究为进一步测试稳定、有效且持久的神经降压素类似物作为潜在的精神安定药提供了背景。 (C) 2000 Elsevier Science B.V. 保留所有权利。
The tridecapeptide neurotensin has long been proposed as an endogenous neuroleptic. However, for neurotensin [or neurotensin(8-13) [NT(8-13)], the active fragment] to cause its effects, it must be administered centrally. Here, we report on an analog of NT(8-13), (N-methyl-Arg),Lys,Pro,L-neo-Trp, tert-Leu,Leu (NT69L), which contains a novel amino acid, L-neo-tryptophan and exhibits high affinity for the rat and human neurotensin receptor, subtype 1. After intraperitoneal (i.p.) injection (1 mg/kg), NT69L induced hypothermia of > 5 degrees C (rectal), with a significant effect persisting for over 7 h. NT69L also caused a rapid (within 15 min) and persistent (for over 5 h) antinociceptive effect, as determined by the hot plate test. NT69L was overall the most potent and longest lasting neurotensin analog that has been reported. These studies provide the background for further testing of a stable, potent and long lasting neurotensin analog as a potential neuroleptic. (C) 2000 Elsevier Science B.V. All rights reserved.