KW-7158

KW-7158 is a tricyclic small molecule belonging to the benzothiepin class. It was developed by Kyowa Hakko Kirin as an orally active investigational drug for the treatment of overactive bladder (OAB), urinary urgency, frequent urination, and urinary incontinence associated with bladder overactivity. Unlike traditional anticholinergic agents used for OAB, KW-7158 acts via a non-cholinergic mechanism. Its therapeutic effect is primarily attributed to suppression of sensory afferent nerves by inhibiting equilibrative nucleoside transporter 1 (ENT1). This inhibition increases extracellular adenosine levels in peripheral c-fibers, which may activate adenosine receptors and/or open A-type potassium channels (Kv channels), leading to reduced excitability of dorsal root ganglion neurons and ultimately suppressing abnormal bladder contractions. The drug reached phase II clinical trials for OAB but development was discontinued.