A computational study of the binding of 3-(arylidene) anabaseines to two major brain nicotinic acetylcholine receptors and to the acetylcholine binding protein.

Nicotinic acetylcholine receptors (nAChRs) have become targets for drug development in recent years. 3-(2,4-dimethoxybenzylidene)-anabaseine (DMXBA), which selectively stimulates the alpha7 nAChR, has been shown to alleviate some cognitive deficits associated with schizophrenia. In this paper we report an analysis of the interactions between 47 arylidene-anabaseines (including 45 benzylidene-anabaseines) and rat brain alpha7 and alpha4beta2 nicotinic acetylcholine receptors, using three different modeling techniques, namely 2D-QSAR, 3D-QSAR and molecular docking to the Aplysia californica acetylcholine binding protein (AChBP), a water soluble, homomeric nAChR surrogate receptor with a known crystal structure.

Nicotinic receptor inhibition by Tetraponera ant alkaloids.

1. Tetraponerines are a group of alkaloids occurring in the venoms of ants belonging to the genus Tetraponera. Eight compounds had been isolated and their structures elucidated, but their mechanisms of action had not yet been reported.

Hydroxy metabolites of the Alzheimer's drug candidate 3-[(2,4-dimethoxy)benzylidene]-anabaseine dihydrochloride (GTS-21): their molecular properties, interactions with brain nicotinic receptors, and brain penetration.

3-[(2,4-dimethoxy)benzylidene]-anabaseine dihydrochloride (DMXBA; GTS-21), an Alzheimer's drug candidate, selectively stimulates alpha7 nicotinic acetylcholine receptors. It rapidly enters the brain after oral administration and enhances cognitive behavior. Less than 1% of orally administered DMXBA is recovered in the urine.