Melatonin: A Comprehensive Review of Pharmacological Uses and Recent Advances

Abstract

Melatonin (N-acetyl-5-methoxytryptamine) is an indoleamine primarily secreted by the pineal gland in response to the dark-light cycle. It plays a pivotal role in the regulation of circadian rhythms and sleep-wake cycles. In recent decades, extensive research has revealed melatonin’s multifaceted physiological and therapeutic effects extending far beyond sleep regulation. It exhibits potent antioxidant and anti-inflammatory properties, modulates immune responses, and supports mitochondrial function, making it a promising candidate for managing a broad spectrum of health conditions. This review provides a comprehensive examination of recent advances in understanding melatonin’s mechanisms of action and its clinical relevance. The hormone influences cellular pathways through both receptor-dependent (MT1 and MT2 receptors) and receptor-independent mechanisms, affecting neuroendocrine signalling, redox balance, and cellular homeostasis. Emerging evidence supports melatonin’s role in the prevention and adjunctive treatment of neurodegenerative diseases such as Alzheimer’s and Parkinson’s, cardiovascular disorders including hypertension and ischemia-reperfusion injury, metabolic diseases like obesity and type 2 diabetes, and various cancers where it exhibits antiproliferative, antiangiogenic, and pro-apoptotic effects. Furthermore, the review explores pharmaceutical advancements in melatonin delivery systems, its safety profile, pharmacokinetics, and regulatory considerations across different countries. Given its low toxicity, wide therapeutic index, and synergistic potential with conventional therapies, melatonin is increasingly recognized as a valuable component in integrative medical strategies. Overall, the paper emphasizes the importance of continued research into melatonin’s diverse biological roles and its optimization as a therapeutic agent in clinical practice.