KRM-II-81

KRM-II-81 is a novel small molecule classified as an imidazodiazepine and positive allosteric modulator (PAM) of the GABA~A~ receptor, with subtype selectivity for α2- and α3-containing GABA~A~ receptors. It is designed to be orally bioavailable and displays anticonvulsant, anxiolytic, antinociceptive, and antidepressant-like activity in preclinical models. KRM-II-81 is notable for broad anti-seizure efficacy including in pharmaco-resistant epilepsy models and tissue, with a low risk of tolerance, dependence, sedation, motor impairment, and abuse liability relative to classical benzodiazepines. It produces its therapeutic effects by preferentially potentiating α2- and α3-GABA~A~ receptors, which are targeted for improved anticonvulsant and anxiolytic profiles, avoiding the side effects commonly seen with α1-selective agents. KRM-II-81 increases IPSC decay time, leading to enhanced inhibitory neurotransmission and increased seizure thresholds. The compound is in IND-enabling studies and has structural analogs moving into clinical development. Developers are preparing clinical GMP-grade material, with studies indicating both oral and intravenous (as a hydrochloride salt) bioavailability and high CNS penetration, which supports its clinical translation for epilepsy and pain indications[1][2][3][4][5][6][7][8].

Other names

KRM-II-81KRM-II81KRM-II 81