Therapeutic treatments potentially mediated by melatonin receptors: potential clinical uses in the prevention of osteoporosis, cancer and as an adjuvant therapy

Abstract

: Melatonin's therapeutic potential is grossly underestimated because its functional roles are diverse and its mechanism(s) of action are complex and varied. Melatonin produces cellular effects via a variety of mechanisms in a receptor independent and dependent manner. In addition, melatonin is a chronobiotic agent secreted from the pineal gland during the hours of darkness. This diurnal release of melatonin impacts the sensitivity of melatonin receptors throughout a 24‐hr period. This changing sensitivity probably contributes to the narrow therapeutic window for use of melatonin in treating sleep disorders, that is, at the light‐to‐dark (dusk) or dark‐to‐light (dawn) transition states. In addition to the cyclic changes in melatonin receptors, many genes cycle over the 24‐hr period, independent or dependent upon the light/dark cycle. Interestingly, many of these genes support a role for melatonin in modulating metabolic and cardiovascular physiology as well as bone metabolism and immune function and detoxification of chemical agents and cancer reduction. Melatonin also enhances the actions of a variety of drugs or hormones; however, the role of melatonin receptors in modulating these processes is not known. The goal of this review is to summarize the evidence related to the utility of melatonin as a therapeutic agent by focusing on its other potential uses besides sleep disorders. In particular, its use in cancer prevention, osteoporosis and, as an adjuvant to other therapies are discussed. Also, the role that melatonin and, particularly, its receptors play in these processes are highlighted.

An insight into the scientific background and future perspectives for the potential uses of melatonin

“…Melatonin plays a regulatory role in many physiological processes including bone metabolism [140]. Melatonin may affect bone metabolism through bone anabolic as well as antiresorptive effects.…”

Melatonin signaling in mouse cerebellar granule cells with variable native MT1 and MT2 melatonin receptors

“…The nanomolar concentrations of melatonin act on the G protein-coupled melatonin receptors MT1 and MT2 (formerly known as Mel1a and Mel1b) (Dubocovich et al, 2003;Witt-Enderby et al, 2006). These receptors, which typically are linked to the inhibition of cAMP-mediated signaling, are expressed in various types of mammalian neurons including in the human brain (Brunner et al, 2006;Jimenez-Jorge et al, 2007;Savaskan et al, 2002Savaskan et al, , 2005Thomas et al, 2002;Uz et al, 2005;Wu et al, 2006Wu et al, , 2007.…”

Crystal structure of methyl 5-methoxy 1H-indole-2-carboxylate, C11H11NO3

“…MLT appears to have sleep-inducing properties in addition to the other e ects reported in the literature like anti-in ammatory, pain modulatory, antitumor and antioxidant properties [2][3][4][5]. MLT exerts its e ects via manipulation of two G-protein-coupled receptors, namely MT1 and MT 2 receptors as well as a low-a nity putative MLT binding site called MT 3 [6,7].…”