PNU-120596  (Synonyms: NSC 216666)

PNU-120596 (NSC 216666) is a potent and selective α7 nAChR positive allosteric modulator (PMA) 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].

EC50: 216 nM (α7 nAChR)^[1]

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

311.72

Solid

C₁₃H₁₄ClN₃O₄

501925-31-1

O=C(NC1=CC(Cl)=C(C=C1OC)OC)NC2=NOC(C)=C2

Room temperature in continental US; may vary elsewhere.

• [1]. Hurst RS, et al. A novel positive allosteric modulator of the alpha7 neuronal nicotinic acetylcholine receptor: in vitro and in vivo characterization. J Neurosci, 2005, 25(17), 4396-4405.  [Content Brief]

  [2]. Barron SC, et al. An allosteric modulator of alpha7 nicotinic receptors, N-(5-Chloro-2,4-dimethoxyphenyl)-N'-(5-methyl-3-isoxazolyl)-urea (PNU-120596), causes conformational changes in the extracellular ligand binding domain similar to those caused by ace  [Content Brief]

  [3]. Munro G, et al. The α7 nicotinic ACh receptor agonist compound B and positive allosteric modulator PNU-120596 both alleviate inflammatory hyperalgesia and cytokine release in the rat. Br J Pharmacol, 2012, doi: 10.1111/j.1476-5381.2012.02003.x  [Content Brief]