Isoanatabine, a naturally occurring α4β2 nicotinic receptor agonist

Pyridine alkaloids with activity in the central nervous system

“… 196 These findings indicate that isoanatabine is a more potent ACh stimulant at the α4β2-receptors relative to anabasine and anatabine, suggesting the presence and the position of the double bond improves nicotinic receptor binding. 196

Fig. 30 Isoanatabine.

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“…30 ) was isolated from the hoplonemertine Amphiporus anagulatus by Kem and co-workers in 2009. 196 This alkaloid is an anatabine isomer possessing a carbon–carbon double bond in the 3,4-position of the piperidine scaffold. 48 , 196 The naturally occurring enantiomeric form of isoanatabine has not yet been reported.…”

“… 196 This alkaloid is an anatabine isomer possessing a carbon–carbon double bond in the 3,4-position of the piperidine scaffold. 48 , 196 The naturally occurring enantiomeric form of isoanatabine has not yet been reported. Due to the structural similarity with nicotine, the pharmacological properties of both (−)- and (+)-isoanatabine were examined by Kem and co-workers at rat and human α4β2-nAChRs.…”

“…Due to the structural similarity with nicotine, the pharmacological properties of both (−)- and (+)-isoanatabine were examined by Kem and co-workers at rat and human α4β2-nAChRs. 196 The binding affinity of (−)-isoanatabine (K i = 108 nM) at rat α4β2-nAChR was slightly stronger than the (+)-enantiomer (K i = 136 nM); however, at the human α4β2-nAChR, (−)-isoanatabine was less efficacious (EC 50 = 1.01 µM; I max = 78.7%) than the (+)-enantiomer (EC 50 = 0.31 µM; I max = 102%). 196 These findings indicate that isoanatabine is a more potent ACh stimulant at the α4β2-receptors relative to anabasine and anatabine, suggesting the presence and the position of the double bond improves nicotinic receptor binding.…”