PNU-120596

PNU-120596 (NSC 216666) is a potent and selective α7 nAChR positive allosteric modulator (PMA) that can cross the blood-brain barrier, with an EC₅₀ of 216 nM. PNU-120596 is inactive against α4β2, α3β4, and α9α10 nAChRs. PNU-120596 has the potential for psychiatric and neurological disorders research^[1]. IC50 & Target:EC50: 216 nM (α7 nAChR)^[1] In Vitro:PNU-120596 increases agonist-evoked calcium flux mediated by an engineered variant of the human α7 nAChR. Electrophysiology studies confirme that PNU-120596 increases peak agonist-evoked currents mediated by wild-type receptors and also demonstrates a pronounced prolongation of the evoked response in the continued presence of agonist. PNU-120596 increases the channel mean open time of α7 nAChRs^[1].
When applied to acute hippocampal slices, PNU-120596 increases the frequency of ACh-evoked GABAergic postsynaptic currents measured in pyramidal neurons^[1].
PNU-120596 enhances agonist-evoked gating of nicotinic receptors by eliciting conformational effects that are similar but nonidentical to the gating conformations promoted by ACh^[2]. In Vivo:PNU-120596 (1 mg/kg; intravenous injection; once) treatment improves the auditory gating deficit caused by Amphetamine in rats, a model proposed to reflect a circuit level disturbance associated with schizophrenia^[1].
When administered before carrageenan, NU-120596 (30 mg/kg; i.p.) significantly reduces mechanical hyperalgesia and weight-bearing deficits for up to 4 h in Sprague-Dawley rats. PNU-120596 attenuates the carrageenan-induced increase in levels of TNF-α and IL-6 within the hind paw oedema^[3].