Aporphine metho salts as neuronal nicotinic acetylcholine receptor blockers

Natural compounds boldine and menthol are antagonists of human 5‐HT3 receptors: implications for treating gastrointestinal disorders

“…Boldine has been traditionally used for treating GI disorders especially by South American natives and it also mediates a smooth muscle relaxation in the GI tract . Among its known pharmacological targets are metabotropic dopamine‐ and 5‐HT 2A receptors, and ligand‐gated neuronal nACh receptors …”

Nitrogen-Containing Constituents of Black Cohosh: Chemistry, Structure Elucidation, and Biological Activities

“…Aporphinoids also act as α-adrenergic antagonists [83], and those with quaternary nitrogen have affinity for neuronal nicotinic receptors. For example, xanthoplanine ( 35 ) bound to the α4β2 subtype of nicotinic receptors with a K i of 0.91 µM [84]. Overall, as a class, aporphinoids are likely to contribute significantly to the overall pharmacological profile of black cohosh and are strong candidates for inclusion in the standardization process.…”

Monoaminergic, Ion Channel and Enzyme Inhibitory Activities of Natural Aporphines, their Analogues and Derivatives

“…To the best of our knowledge, boldine and a couple of its brominated derivatives are the only aporphines that have been tested as nicotinic cholinergic ligands. Their affinities for neuronal nicotinic acetylcholine receptors (nAChR), an important family of ligandgated cation channels, decrease on going from the 3bromo-to the 3,8-dibromo compound, suggesting that halogenation is not a useful approach to obtain more active nAChR blockers [75] (Table 4).…”

“…A study dating back to 1975 showed that the metho salts of the natural (6aS)(+)-corydine, isocorydine, glaucine, and boldine, are slightly more potent than their unnatural enantiomers at the neuromuscular junction [76]. Quite recently it was shown that the methiodides of boldine, predicentrine, glaucine, 3-bromo-and 3,8-dibromo-boldine, and xanthoplanine iodide (the methiodide of N-methyllaurotetanine) also block neuronal nicotinic acetylcholine receptors at low micromolar concentrations, with slight (2 to 20-fold) selectivity for the α4β2 over the α7 subtype [75] ( Table 5).…”

“…Binding affinities of some quaternary and tertiary (6aS)aporphines for the major (cloned human) central nervous system nicotinc acetylcholine receptor subtypes[75].…”