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Review
. 2018 Dec 23;9(1):6.
doi: 10.3390/biom9010006.

Epibatidine: A Promising Natural Alkaloid in Health

Bahare Salehi  1 , Simona Sestito  2 , Simona Rapposelli  3   4 , Gregorio Peron  5 , Daniela Calina  6 , Mehdi Sharifi-Rad  7 , Farukh Sharopov  8 , Natália Martins  9   10 , Javad Sharifi-Rad  11   12
Affiliations
Review

Epibatidine: A Promising Natural Alkaloid in Health

Bahare Salehi et al. Biomolecules. .

Abstract

Epibatidine is a natural alkaloid that acts at nicotinic acetylcholine receptors (nAChRs). The present review aims to carefully discuss the affinity of epibatidine and its synthetic derivatives, analogues to nAChRs for α4β2 subtype, pharmacokinetic parameters, and its role in health. Published literature shows a low affinity and lack of binding of epibatidine and its synthetic analogues to plasma proteins, indicating their availability for metabolism. Because of its high toxicity, the therapeutic use of epibatidine is hampered. However, new synthetic analogs endowed from this molecule have been developed, with a better therapeutic window and improved selectivity. All these aspects are also discussed here. On the other hand, many reports are devoted to structure⁻activity relationships to obtain optically active epibatidine and its analogues, and to access its pharmacological effects. Although pharmacological results are obtained from experimental studies and only a few clinical trials, new perspectives are open for the discovery of new drug therapies.

Keywords: ABT-418; ABT-594; analgesics; epibatidine; nicotinic acetylcholine receptors.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structure of flubatine (up) and charge distribution for the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) states (down). Methods: The ab initio calculations were performed with Gaussian 16w B.01 and modeled with GaussView 6.0.16 (Andreescu Labor Soft S.R.L., Bucharest, Romania). The optimization of the molecule and HOMO and LUMO states were calculated based on semi-empirical method PM6. It is easy to observe that the fluorine atom, for the HOMO statehas a positive charge; all the electrons are attracted on the rings. On LUMO state, the fluorine atom is partially shielded.
Figure 2
Figure 2
Epibatidine and its analogues.
See this image and copyright information in PMC

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