Search PubMed⌕ Search

PubMed · 15050621

Epibatidine structure-activity relationships.

Abstract

Epibatidine is a potent but nonselective nAChR agonist. Its biological effects appear to be mediated largely by alpha4beta2 nAChRs. Surprisingly, only a limited number of epibatidine analogues have been synthesized and evaluated in in vitro assays. Even fewer analogues have received in vivo pharmacological evaluation. In this paper, SAR studies directed toward epibatidine analogues will be reviewed.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

F Ivy Carroll. 2004-04-19. Epibatidine structure-activity relationships.. https://doi.org/10.1016/j.bmcl.2004.02.007

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

A practical synthesis of (+/-)-alpha-isosparteine from a tetraoxobispidine core.

[reaction: see text] The title alkaloid was synthesized in racemic form from 3,7-diallyl-2,4,6,8-tetraoxo-3,7-diazabicyclo[3.3.1]nonane (7) by a regioselective diallylation reaction followed by double ring-closing olefin metathesis and exhaustive reduction. Tetraoxobispidine 7 was itself prepared in three simple operations from dimethyl malonate. The entire sequence to alpha-isosparteine was conducted on a multigram scale and proceeded without recourse to chromatography.

Bridged Bicyclo Compounds, Heterocyclic↗

Photoactivation of GFP reveals protein dynamics within the endoplasmic reticulum membrane.

Components of the plant cell secretory pathway, including the endoplasmic reticulum and Golgi apparatus, are in constant motion. The photoactivation of GFP has been used to determine that proteins within the membrane of the ER flow as the ER is remodelled. Measurement of the rate at which activated GFP moves away from the activation spot shows that this motion is much faster than would be expected if membrane components moved simply by diffusion. Treatment with latrunculin to depolymerize the actin cytoskeleton stops ER remodelling and reduces the rate of GFP movement to that expected from diffusion alone. This suggests that myosin binds directly or indirectly to ER membrane proteins and actively moves them around over the actin scaffold. Tracking of Golgi body movement was used to demonstrate that they move at the same rate and in the same direction as do photoactivated ER surface proteins. Golgi bodies, therefore, move with, and not over, the surface of the ER. These observations support the current theory of continuity between Golgi bodies and discrete ER exit sites in the ER membrane.

Bridged Bicyclo Compounds, Heterocyclic↗

Epibatidine analogues as selective ligands for the alpha(x)beta2-containing subtypes of nicotinic acetylcholine receptors.

A series of epibatidine analogues was synthesized and characterized in vitro. These compounds are high affinity ligands for the nicotinic acetylcholine receptors (nAChR). They display binding selectivity for the alpha(x)beta2 subtypes of nAChRs over the alpha(x)beta4 subtypes, and especially for the alpha4beta2 and alpha2beta2 subtypes. Furthermore, most of these new nicotinic compounds display little, if any, agonist activities at alpha3beta4 nAChR. As a result they might become lead structures for the design and synthesis of highly selective ligands for nAChR subtypes containing the beta2 subunit.

Bridged Bicyclo Compounds, Heterocyclic↗