Delta Opioid Receptor (DOR) Ligands and Pharmacology: Development of Indolo- and Quinolinomorphinan Derivatives Based on the Message-Address Concept.
Delta Opioid Receptor (DOR) Ligands and Pharmacology: Development of Indolo- and Quinolinomorphinan Derivatives Based on the Message-Address Concept.
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Delta 阿片受体 (DOR) 配体和药理学：基于消息地址概念开发吲哚和喹啉吗啡喃衍生物。
DOI：
10.1007/164_2016_18
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发表时间：
2018
影响因子：
--
通讯作者：
H. Nagase
中科院分区：
文献类型：
--
作者：
A. Saitoh;H. Nagase
δ阿片受体（DOR）的药理学已经滞后，主要是由于缺乏一种在体内具有高效力和选择性的激动剂。DOR正受到越来越多的关注，并且在合成更好的新型配体方面已经取得了进展。选择性DOR受体拮抗剂纳曲吲哚（naltrindole，NTI）的发现促进了（±）TAN-67的设计和合成。使用（±）TAN-67的深入研究确定了DOR介导的各种药理学作用，如疼痛性糖尿病神经病变的抗伤害作用和心血管保护作用。我们改进了TAN-67的激动剂活性，得到SN-28，其被修饰为KNT-127，一种改善血脑屏障通透性的新化合物。此外，KNT-127对DOR显示出更高的选择性，并且在全身给药后具有有效的激动剂活性。有趣的是，与原型DOR激动剂不同，KNT-127不产生惊厥作用。具有喹啉吗啡喃结构的KNT-127型衍生物有望成为开发治疗性DOR激动剂的有前途的候选物。
The pharmacology of the delta opioid receptor (DOR) has lagged, mainly due to the lack of an agonist with high potency and selectivity in vivo. The DOR is now receiving increasing attention, and there has been progress in the synthesis of better novel ligands. The discovery of a selective receptor DOR antagonist, naltrindole (NTI), stimulated the design and synthesis of (±)TAN-67, which was designed based on the message-address concept and the accessory site theory. Intensive studies using (±)TAN-67 determined the DOR-mediated various pharmacological effects, such as antinociceptive effects for painful diabetic neuropathy and cardiovascular protective effects. We improved the agonist activity of TAN-67 to afford SN-28, which was modified to KNT-127, a novel compound that improved the blood-brain barrier permeability. In addition, KNT-127 showed higher selectivity for the DOR and had potent agonist activity following systemic administration. Interestingly, KNT-127 produced no convulsive effects, unlike prototype DOR agonists. The KNT-127 type derivatives with a quinolinomorphinan structure are expected to be promising candidates for the development of therapeutic DOR agonists.
Kappa-和δ-阿片类药物可阻断交感神经依赖性痛觉过敏。
DOI：
10.1523/jneurosci.11-04-00928.1991
发表时间：
1991
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Taiwo,YO;Levine,JD
通讯作者：
Levine,JD
DOI：
--
发表时间：
1994-09
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
S. Negus;E. Butelman;K. Chang;B. Decosta;G. Winger;J. Woods
通讯作者：
S. Negus;E. Butelman;K. Chang;B. Decosta;G. Winger;J. Woods
小鼠全身给予 δ 阿片受体激动剂 BW373U86 的惊厥作用。
DOI：
--
发表时间：
1993
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Comer,SD;Hoenicke,EM;Sable,AI;McNutt,RW;Chang,KJ;DeCosta,BR;Mosberg,HI;Woods,JH
通讯作者：
Woods,JH