EPIBATIDINE: FROM FROG ALKALOID TO ANALGESIC CLINICAL CANDIDATES. A TESTIMONIAL TO "TRUE GRIT"!

被引：19

作者：

Garraffo, H. Martin ^{[1
]}

Spande, Thomas F. ^{[1
]}

Williams, Michael ^{[2
]}

机构：

[1] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA

[2] Cephalon Inc, Discovery Res, W Chester, PA USA

来源：

HETEROCYCLES | 2009年 / 79卷

关键词：

Poison Frog; Alkaloid; Epibatidine; Nicotinic Agonist; Straub-Tail; NICOTINIC ACETYLCHOLINE-RECEPTORS; IN-VITRO; POTENT; CHEMISTRY; DISCOVERY; AGONIST; ABT-594; ABT-418; LIGAND; SKIN;

D O I：

10.3987/REV-08-SR(D)5

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A routine toxicity test of the alkaloid extract from the Ecuadoran poison frog Epipedobates anthonyi gave a Straub-tail (S-T) response on sub-cutaneous (sc) injection in mice, a phenomenon never seen before from any poison frog alkaloid. It is characteristic of opioids; however, in this instance it was not blocked by a morphine-antagonist, naloxone. Its site of action was soon shown to be a nicotinic receptor. The determination of the structure of this novel analgesic named epibatidine has led to a renaissance of research into controlling pain via nicotinic pathways (thereby minimizing the risk of tolerance/addiction) and the synthesis of many analogs, some of which are discussed.

引用

页码：207 / 217

页数：11

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