Melatonin

Reducing the toxicity and increasing the efficacy of drugs

Russel J Reiter, Dun Xian Tan, Rosa M. Sainz, Juan C. Mayo, Silvia Lopez-Burillo

Research output: Contribution to journalArticle

333 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1299-1321
Number of pages23
JournalJournal of Pharmacy and Pharmacology
Volume54
Issue number10
DOIs
StatePublished - Oct 1 2002

Fingerprint

Melatonin
Pharmaceutical Preparations
Body Fluid Compartments
5-Methoxytryptamine
Plant Dispersal
Epirubicin
Free Radical Scavengers
Ranitidine
Omeprazole
Cytarabine
Isoniazid
Carbamazepine
Bleomycin
Haloperidol
Phenobarbital
Erythropoietin
Gentamicins
Drug-Related Side Effects and Adverse Reactions
Indomethacin
Doxorubicin

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Melatonin : Reducing the toxicity and increasing the efficacy of drugs. / Reiter, Russel J; Tan, Dun Xian; Sainz, Rosa M.; Mayo, Juan C.; Lopez-Burillo, Silvia.

In: Journal of Pharmacy and Pharmacology, Vol. 54, No. 10, 01.10.2002, p. 1299-1321.

Research output: Contribution to journalArticle

Reiter, Russel J ; Tan, Dun Xian ; Sainz, Rosa M. ; Mayo, Juan C. ; Lopez-Burillo, Silvia. / Melatonin : Reducing the toxicity and increasing the efficacy of drugs. In: Journal of Pharmacy and Pharmacology. 2002 ; Vol. 54, No. 10. pp. 1299-1321.
@article{ecc9a23ad8494899966311a51f3c62fe,
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.",
author = "Reiter, {Russel J} and Tan, {Dun Xian} and Sainz, {Rosa M.} and Mayo, {Juan C.} and Silvia Lopez-Burillo",
year = "2002",
month = "10",
day = "1",
doi = "10.1211/002235702760345374",
language = "English (US)",
volume = "54",
pages = "1299--1321",
journal = "Journal of Pharmacy and Pharmacology",
issn = "0022-3573",
publisher = "Pharmaceutical Press",
number = "10",

}

TY - JOUR

T1 - Melatonin

T2 - Reducing the toxicity and increasing the efficacy of drugs

AU - Reiter, Russel J

AU - Tan, Dun Xian

AU - Sainz, Rosa M.

AU - Mayo, Juan C.

AU - Lopez-Burillo, Silvia

PY - 2002/10/1

Y1 - 2002/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0036797512&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036797512&partnerID=8YFLogxK

U2 - 10.1211/002235702760345374

DO - 10.1211/002235702760345374

M3 - Article

VL - 54

SP - 1299

EP - 1321

JO - Journal of Pharmacy and Pharmacology

JF - Journal of Pharmacy and Pharmacology

SN - 0022-3573

IS - 10

ER -