JNJ-78911118 is a potent, brain-penetrant, selective GluN2A antagonist ( IC50 = 44 nM). JNJ-78911118 shows >200-fold selectivity against GluN1/2B, 2C and 2D receptors. JNJ-78911118 functions as a negative allosteric modulator (NAM) by insurmountably suppressing glutamate efficacy and reducing glycine potency at GluN1/2A receptors. JNJ-78911118 produces profound pharmacodynamic effects in vivo. JNJ-78911118 can be used for depression research [1].
In Vivo, JNJ-78911118 (60 mg/kg, s.c., single dose) mitigates mechanical allodynia in the Complete Freund's adjuvant (CFA) mouse models of inflammatory pain, prevents hippocampal long-term potentiation (LTP) in rats and increases miniature excitatory postsynaptic current (mEPSC) frequency in the rat prefrontal cortex[1]. JNJ-78911118 (50 and 250 mg/kg, p.o., twice daily for 4 days or twice on the same day) is generally well tolerated but produces dose-related haemodynamic effects in rats[1].
In Vitro, JNJ-78911118 (10 pM-10 μM, 2 h) displaces the GluN1/2A interface binding radioligand JNJ-74950343 in hippocampal neuron membranes in a concentration-dependent manner, and does not alter glutamate potency but reduces its efficacy against homomeric GluN1/2A receptors[1]. JNJ-78911118 (10 μM, 24-72 h) promotes neurite outgrowth and synaptogenesis in rat hippocampal neuronal cultures, significantly enhancing multiple measures of dendritic complexity after 72 h[1]. JNJ-78911118 (1-10 μM) shows less than 50 % inhibition against all targets in a custom panel of 77 ion channels, receptors, and transporters, as well as a panel of 373 kinases[1].
References:
[1]. Lord B, et al Pharmacological characterisation of JNJ-78911118, a novel, centrally-penetrant, selective GluN2A antagonist. Br J Pharmacol. 2025 Sep;182(17):4080-4102.
In Vivo, JNJ-78911118 (60 mg/kg, s.c., single dose) mitigates mechanical allodynia in the Complete Freund's adjuvant (CFA) mouse models of inflammatory pain, prevents hippocampal long-term potentiation (LTP) in rats and increases miniature excitatory postsynaptic current (mEPSC) frequency in the rat prefrontal cortex[1]. JNJ-78911118 (50 and 250 mg/kg, p.o., twice daily for 4 days or twice on the same day) is generally well tolerated but produces dose-related haemodynamic effects in rats[1].
In Vitro, JNJ-78911118 (10 pM-10 μM, 2 h) displaces the GluN1/2A interface binding radioligand JNJ-74950343 in hippocampal neuron membranes in a concentration-dependent manner, and does not alter glutamate potency but reduces its efficacy against homomeric GluN1/2A receptors[1]. JNJ-78911118 (10 μM, 24-72 h) promotes neurite outgrowth and synaptogenesis in rat hippocampal neuronal cultures, significantly enhancing multiple measures of dendritic complexity after 72 h[1]. JNJ-78911118 (1-10 μM) shows less than 50 % inhibition against all targets in a custom panel of 77 ion channels, receptors, and transporters, as well as a panel of 373 kinases[1].
References:
[1]. Lord B, et al Pharmacological characterisation of JNJ-78911118, a novel, centrally-penetrant, selective GluN2A antagonist. Br J Pharmacol. 2025 Sep;182(17):4080-4102.