Online article for Non-subscribers

Pay per view

Heterocycles has a pay-per-view service for Non-subscribers.
You will be able to directly purchase the full text article through PayPal.
Your purchased Paper can be downloaded after the payment is completed.
An e-mail will be sent the URL to download the paper.
If you have any questions, please contact:

Price: ¥ 4,400 (Yen only)
Period: This Article can be accessed for 7 days.

Review | Special issue | Vol 79, No. 1, 2009, pp.207-217
Published online, 10th December, 2008
DOI: 10.3987/REV-08-SR(D)5
Epibatidine: From Frog Alkaloid to Analgesic Clinical Candidates. A Testimonial to “True Grit”!

H. Martin Garraffo, Thomas F. Spande, and Michael Williams*

*Discovery Research, Cephalon Inc., 145 Brandywine Parkway, West Chester, PA 19380, U.S.A.


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.