PNU-120596 (NSC 216666 ) is a potent and selective positive allosteric α7 nAChR modulator with an EC50 of 0.2 μM. PNU-120596 increased agonist-evoked calcium flux mediated by an engineered variant of the human alpha7 nAChR. PNU-120596 increased peak agonist-evoked currents mediated by wild-type receptors and also demonstrated a pronounced prolongation of the evoked response in the continued presence of agonist. PNU-120596 increased the channel mean open time of alpha7 nAChRs but had no effect on ion selectivity and relatively little, if any, effect on unitary conductance. When applied to acute hippocampal slices, PNU-120596 increased the frequency of ACh-evoked GABAergic postsynaptic currents measured in pyramidal neurons[3]. PNU-120596 enhanced voltage-dependent inhibition of α(7) responses by bicuculline and choline. In the presence of PNU-120596, α(7) channels favored a burst-like kinetic modality in the presence, but not absence of bicuculline and bursts of α(7) openings were voltage-dependent[4]. The PNU 120596 (1 or 4 mg/kg, i.p.) dose-dependently prevented LPS-induced (lipopolysaccharide) depressive-like behavior during FST, TST, FST (forced swim test), TST (tail suspension test) and sucrose preference test. Similarly, the PNU 120596 (4 mg/kg, i.p.) significantly reduced LPS-induced increased expression of Iba-1 in the hippocampus or prefrontal cortex[5].
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