title: Melatonin: reducing the toxicity and increasing the efficacy of drugs.
abstract: Melatonin (N-acetyl-5-methoxytryptamine) is a molecule with a very wide phylogenetic distribution from plants to man. In vertebrates, melatonin was initially thought to be exclusively of pineal origin recent studies have shown, however, that melatonin synthesis may occur in a variety of cells and organs. The concentration of melatonin within body fluids and subcellular compartments varies widely, with blood levels of the indole being lower than those at many other sites. Thus, when defining what constitutes a physiological level of melatonin, it must be defined relative to a specific compartment. Melatonin has been shown to have a variety of functions, and research in the last decade has proven the indole to be both a direct free radical scavenger and indirect antioxidant. Because of these actions, and possibly others that remain to be defined, melatonin has been shown to reduce the toxicity and increase the efficacy of a large number of drugs whose side effects are well documented. Herein, we summarize the beneficial effects of melatonin when combined with the following drugs: doxorubicin, cisplatin, epirubicin, cytarabine, bleomycin, gentamicin, ciclosporin, indometacin, acetylsalicylic acid, ranitidine, omeprazole, isoniazid, iron and erythropoietin, phenobarbital, carbamazepine, haloperidol, caposide-50, morphine, cyclophosphamide and L-cysteine. While the majority of these studies were conducted using animals, a number of the investigations also used man. Considering the low toxicity of melatonin and its ability to reduce the side effects and increase the efficacy of these drugs, its use as a combination therapy with these agents seems important and worthy of pursuit.
authors.affiliation: University of Texas Health Science Center, Department of Cellular and Structural Biology, MC 7762, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. Reiter@uthscsa.edu
authors.forename: Russel J
authors.initials: RJ
authors.lastname: Reiter
authors.forename: Dun-Xian
authors.initials: DX
authors.lastname: Tan
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Sainz
authors.forename: Juan C
authors.initials: JC
authors.lastname: Mayo
authors.forename: Silvia
authors.initials: S
authors.lastname: Lopez-Burillo
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D064420:Drug-Related Side Effects and Adverse Reactions; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D008550:Melatonin / Q000494:pharmacology* / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D008550:Melatonin