Drug Discovery Targeting Nicotinic Acetylcholine Receptors for Hearing Loss.

Hearing loss is detrimental to human health, and currently, more than 1.5 billion people are affected by hearing loss. Active military personnel and construction workers are examples of individuals in the workplace who are exposed to loud noise and are at serious risk of hearing loss. While there is currently no therapy for hearing loss, evidence supports investigating the enhancement of the Medial Olivocochlear (MOC) system, an efferent pathway for hearing that serves as a gain-control for hearing loss protection. Selectively modulating the α9α10 nicotinic acetylcholine receptor (nAChRs) found within this pathway is promising for the development of a new drug class. In this review article, we present the most current findings related to the therapeutic targeting of α9α10 nAChRs for hearing loss. We discuss the loss- or gain-of-function of the receptor, evaluate the known modulators of the receptor, examine their clinical relevance, and discuss their chemical and physical properties. Investigation of this novel pathway may aid in the development of a therapeutic for hearing loss.