Question

Discuss the toxicological models to be used in the development of drug suvorexant. Give particular emphasis to models that will be useful for drug suvorexant and route of delivery

Answer 1

Ans. -

The development of therapeutics for central nervous system (CNS) disorders has many challenges that result in low probability of success and longer-than-typical development timelines. Suvorexant (Belsomra), the first dual orexin receptor antagonist used for insomnia. The utility of Belsomra for insomnia, as well as other neurological and psychiatric diseases, continues to be explored, most recently for insomnia associated with Alzheimer’s disease.

Resion of successful program-

(1) having a robust and high-throughput pharmacodynamic readout that was translatable across species, including humans, (2) a well-validated target with a defined product profile, resulting in a highly energized team with a can-do attitude, and (3) a highly executable and streamlined clinical strategy.

CNS disorders is that disease cannot be easily modeled in preclinical species. For example, measuring neuropsychiatric symptoms such as mood, cognition, or anxiety in preclinical species is not straightforward. Typical preclinical measures of mood in rodents include assays that are sensitive to standard-of-care antidepressants, but the duration of time a mouse struggles when hung by its tail or is placed in a water tank is hardly an assay that would seem an appropriate measure of mood or one that will translate well to humans.

Suvorexant is a potent dual orexin receptor antagonist that blocks both OX1R and OX2R. It promotes sleep through the binding inhibition of orexin A and B, neuropeptides that promote wakefulness. Suovrexant is a novel hypnotic and is the only agent clinically available that works by blocking orexin-ergic mechanisms. Suvorexant exerts its therapeutic effect in insomnia through antagonism of orexin receptors. The orexin neuropeptide signaling system is a central promoter of wakefulness. Blocking the binding of wake-promoting neuropeptides orexin A and orexin B to receptors orexin receptor type 1 (OX1) and orexin receptor type 2 (OX2) is thought to suppress wake drive. Route of drug administration is oral route.