Abstract

This literature review explores in depth the molecular pharmacology and signaling networks in the cochlear microenvironment, a key organ for hearing. The cochlea converts sound vibrations into electrical signals using hair cells and a complex network of receptors and ion channels. Sensorineural hearing loss affects more than 1.5 billion people and is irreversible in adult mammals, underscoring the importance of understanding the molecular mechanisms underlying this condition to develop new therapies. Auditory transduction depends on mechanosensitive channels (TMC1/TMC2) and ionotropic and metabotropic receptors, such as those for glutamate, acetylcholine, dopamine, adenosine, and ATP. These regulate neurotransmission and homeostasis, protecting against damage from noise or ototoxic drugs. Endolymphatic homeostasis, essential for the endocochlear potential, is maintained by the stria vascularis and the spiral ligament, regulated by nuclear and membrane receptors. This review highlights promising pharmacological therapies, such as adenosine A1 agonists (ADAC, CCPA) and P2X/P2Y receptor antagonists, which protect hair cells after noise exposure. Agents such as muscimol (GABA-A) and piribedil (D2/D3) regulate neuronal excitability and prevent excitotoxicity. Glucocorticoids (such as dexamethasone) induce the expression of anti-inflammatory and antioxidant proteins, thereby enhancing cellular resilience. The aim of this review is to characterize the receptors, channels, and signaling pathways in the cochlea, enabling the identification of therapeutic strategies to prevent and treat hearing loss. A thorough understanding of the molecular microenvironment is essential for advancing otoprotective and regenerative solutions that improve the quality of life for those with hearing disorders.