JNJ-55511118

JNJ-55511118 is a selective TARP γ-8 binding AMPA receptor modulator with oral bioavailability and blood-brain barrier permeability, with a K_i of 26 nM. JNJ-55511118 reduces voluntary intake of sweetened alcohol in male mice. In rodent models, JNJ-55511118 inhibits hippocampal neurotransmission, reduces specific electroencephalogram frequency bands, induces transient hyperlocomotion, impairs learning and memory abilities, and exerts anticonvulsant effects. JNJ-55511118 is applicable to research related to alcohol use disorder and seizures^[1][2]. In Vitro:JNJ-55511118 is a potent, selective negative modulator of TARP-γ8-containing AMPA receptors, with a mean pIC₅₀ value ranging from 7.42 to 8.33 across human, rat, mouse, monkey, and canine GluA-γ8 combinations, and it shows no activity against TARP-containing AMPA receptors without γ8 or TARP-free AMPA receptors^[2].
JNJ-55511118 (1 μM; 50-60 s) partially inhibits glutamate-evoked currents in heterologously expressed TARP-γ8-containing AMPA receptors by accelerating desensitization and inactivation processes^[2].
JNJ-55511118 (1 μM; IC₅₀ 6 μM) exerts weak antagonistic activity against human 5-HT₂B receptors (IC₅₀ = 6 μM)^[2]. In Vivo:JNJ-55511118 (0-10 mg/kg; p.o.; single administration) significantly reduces multiple indices of voluntary sweet wine intake in male C57BL/6J mice, without decreasing parameters related to voluntary sweet wine consumption in female C57BL/6J mice, but the 10 mg/kg dose alters lever discrimination behavior by increasing the number of responses on the inactive lever^[1].
JNJ-55511118 (i.v./p.o., 0-10 mg/kg, single administration) dose-dependently suppresses population spikes in the hippocampal CA1 region in anesthetized rats, with an ED₅₀ of 0.4 mg/kg for intravenous injection. It also dose-dependently reduces cortical electroencephalogram power across multiple frequency bands in freely moving rats, and transient hyperactivity occurs at the oral dose of 10 mg/kg^[2].
JNJ-55511118 (p.o.; single dose, 0-40 mg/kg) exerts potent, near-complete seizure protection in corneal and amygdala-kindled mouse models, with an oral ED₅₀ of 3.7 mg/kg. It produces partially dose-dependent seizure protection in the 6 Hz psychomotor seizure model of *Mus musculus*, with ED₅₀ values of 18.3 mg/kg p.o. (32 mA) and 6.5 mg/kg p.o. (44 mA), respectively, and elevates the convulsive threshold of mice to PTZ^[2].