Applications of H3 Receptor Antagonists

ABT-239 (5), a potent H3R antagonist, was effective at low doses (0.1 mg/kg s.c.) in a repeat trial inhibitory avoidance task in SHR pups [26], a model involving aspects of attention, impulsivity and learning that is thought to be relevant to characteristics of ADHD. ABT-239 was active in a social recognition 

Conflicting evidence exists with both agonists and antagonists in pain models that confound the potential role of H3 antagonists in analgesia [12,32]. The H3 

An early biphenyl candidate, A-331440 (6) has been reported to be a competitive, potent inverse agonist with balanced activity at human and rat H3Rs with good oral bioavailability [40]. While A-331440 was active in obesity models, its development was precluded by genotoxicity issues [41], The latter was eliminated by a tactical orf/zo-substitution on the phenoxy central core by fluorine to provide A-417022 (7). A-417022 and the 3,5-difluoro analog (A-423579) also produced prolonged weight loss over a 28-day period in a rat diet-induced obesity model [17,41], 

---