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Overview
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Background
PNU-120596 is a positive allosteric modulator of α7 neuronal nicotinic acetylcholine receptor (nAChR) [1].
PNU-120596 is a type 2 PAM. In cell-based assay, PNU-120596 significantly increases the Ca2+-mediated signal at the concentration of 3μM. It enhances the ACh-evoked Ca22+ flux with EC50 value of 216nM in SH-EP1 cells. PNU-120596 also markedly increases the agonist-evoked currents as well as the current duration in Xenopus oocytes. PNU-120596 is specific to α7nAChR over other neuronal nicotinic acetylcholine receptors. PNU-120596 also potentiates the ACh responses mediated byα7nAChRs in rat hippocampal interneurons. It is considered that PNU-120596 modulates the ACh-dependent increase via enhancing the excitatory effect of ACh on GABAergic interneurons. Furthermore, PNU-120596 is found to improve performance in rodent recognition memory model with increasing the phosphorylation of CREB [1, 2].[1] Hurst R S, Hajós M, Raggenbass M, et al. A novel positive allosteric modulator of the α7 neuronal nicotinic acetylcholine receptor: in vitro and in vivo characterization. The Journal of neuroscience, 2005, 25(17): 4396-4405.
[2] Bertrand D, Gopalakrishnan M. Allosteric modulation of nicotinic acetylcholine receptors. Biochemical pharmacology, 2007, 74(8): 1155-1163.
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