FR-II-60

**FR-II-60** is a novel imidazodiazepine analog of the GABAA receptor potentiator KRM-II-81, designed as a backup compound with a 2'-Cl-phenyl substitution replacing the pyridinyl group. It acts as a **GABAA receptor agonist**, binding to brain GABAA receptors and exhibiting anticonvulsant activity in preclinical rodent models, including protection against maximal electroshock (MES)-induced and 6 Hz-induced seizures following intraperitoneal administration. FR-II-60 demonstrates oral bioavailability but reduced plasma and brain exposure compared to KRM-II-81, along with a lower propensity for sedative effects due to minimized interaction with the α1His102 binding site, as shown in molecular docking studies. Synthesized by the JM Cook Laboratory, it was initially developed by the **University of Wisconsin-Milwaukee** and remains in the **preclinical** stage, with potential applications in epilepsy and related disorders given its efficacy profile.[1][3]