KPP-III-34

**KPP-III-34** is a novel small molecule GABAkine and structural analog of KRM-II-81, designed as a positive allosteric modulator (PAM) of **GABAA receptors** with preferential efficacy at **α2/α3** subtypes and reduced binding to the **α1His102** residue associated with sedation. Developed by researchers at the University of Wisconsin-Milwaukee, it demonstrates **oral bioavailability**, potent **anticonvulsant activity** in rodent models including maximal electroshock (MES), 6 Hz psychomotor seizures, pentylenetetrazol (PTZ)-induced convulsions, corneal-kindled seizures, hippocampal paroxysmal discharges in mesial temporal lobe epilepsy models, and efficacy in **pharmacoresistant epilepsy** models such as lamotrigine-resistant seizures and non-convulsive status epilepticus. It shows low sensorimotor impairment even at high doses (up to 500 mg/kg in rats), distinguishing it from classical benzodiazepines, and is currently in **preclinical development**.[1][4][5][7]