Cardioprotective Melatonin: Translating from Proof-of-Concept Studies to Therapeutic Use
Abstract
:1. Introduction
2. Clinical Trials with Melatonin in Heart Diseases
2.1. Acute Coronary Syndrome
2.2. Coronary Artery Disease
2.3. Cardiac Arrhythmias
2.4. Heart Failure
2.5. Hypertension
2.6. Melatonin Receptor Agonists
3. Evaluation of Melatonin Cardiovascular Target Tractability and Prediction Using Machine Learning on ChEMBL
4. Conclusions and Further Directions
Supplementary Materials
Funding
Acknowledgments
Conflicts of Interest
References
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Target Disease, Reference | Objective | Study Phase | Study Design | Melatonin dosing | Outcomes |
---|---|---|---|---|---|
Myocardial Infarction [12] | Melatonin Adjunct in the Acute myocaRdial Infarction Treated With Angioplasty (MARIA)/NCT00640094 | 2 | randomized, double-blind, placebo controlled trial | Intravenous and intracoronary melatonin during primary percutaneous coronary intervention (PPCI). | Negative: melatonin in patients with STEMI was not associated with a reduction in infarct size and has an unfavourable effect on the ventricular volumes and LVEF evolution |
ST-Elevation Myocardial Infarction (STEMI) [13] | Post hoc of MARIA study/NCT00640094 | 2 | randomized, double-blind, placebo controlled trial | Positive: melatonin in patients with STEMI who presented early after symptom onset was associated with a significant reduction in the infarct size after pPCI | |
Coronary artery bypass grafting [14] | Efficacy of melatonin in reducing early reperfusion injury and acute oxidative stress in patients undergoing coronary artery bypass grafting (CABG). | 2 | randomized, open-label, placebo-controlled trial | Positive: melatonin significantly reduced CABG related cardiac injury and oxidative stress. | |
ST-Elevation Myocardial Infarction (STEMI) [15] | To study whether the administration of melatonin during acute myocardial reperfusion improves myocardial salvage assessed by cardiac magnetic resonance imaging (CMR) in patients with STEMI | 2 | randomized, double-blinded, placebo controlled trial | intracoronary or intravenous melatonin (total 50 mg) | Negative: melatonin did not improve the myocardial salvage index. |
Elective abdominal aortic aneurism repair [16] | To study the effect of perioperative melatonin treatment on clinical cardiac morbidity and markers of myocardial ischemia in patients undergoing elective surgery for abdominal aortic aneurism | randomized, placebo-controlled, clinical trial | infusion over a 2-hr period either, 50 mg melatonin or placebo intra-operatively, and 10 mg melatonin or placebo orally, the first three nights after surgery. | Positive: melatonin decreased clinical cardiac morbidity and the occurrence of myocardial ischemia after abdominal aortic aneurism repair. | |
Postural tachycardia syndrome (POTS) [17] | Tested the hypothesis that melatonin will attenuate the tachycardia and improve symptom burden in patients with POTS. NCT00262470 | 2 | randomized, single-blinded, crossover trial | melatonin 3 mg orally and placebo, on separate mornings, in a randomized crossover design | Negative: There was no significant difference in the reduction of systolic blood pressure between melatonin and placebo, either with standing or while seated. The symptom burden was not improved with melatonin compared with placebo. |
Coronary artery bypass grafting surgery (CABG) [18] | To investigate the effects of Melatoninon nuclear erythroid 2-related factor 2(Nrf2) activity in patients undergoing CABG surgery | 2 | randomized triple-blind placebo-controlled trial | 10 mg oral melatonin (Melatonin group, n = 15) or placebo (placebo group, n = 15) before sleeping for 1 month before surgery | Positive: Increase by melatonin of nuclear erythroid 2-related factor 2(Nrf2) activity in patients undergoing CABG surgery. |
Blood coagulation activity [19] | To investigate if oral administration of melatonin is associated with decreased plasma levels of procoagulant hemostatic measures | 2 | randomized, placebo-controlled, single-blinded trial | 3 mg of oral melatonin or placebo, and one hour thereafter, levels of melatonin, fibrinogen, and D-dimer as well as activities of coagulation factor VII (FVII:C) and VIII (FVIII:C) were measured in plasma | Positive: lower levels of the coagulation measures FVIII:C and fibrinogen one hour after oral intake of a single dose of 3 mg of melatonin compared to placebo medication. Suggested potential implications for the use of melatonin as a theapeutic agent in patients at-risk of atherothrombotic events such as patients with CAD or systemic hypertension |
ChEMBL ID | Name | Synonyms | Max Phase | Molecular Weight | QED Weighted | Mesh_Heading |
---|---|---|---|---|---|---|
CHEMBL45 | MELATONIN | Circadin, General Nutrit, Health Aid, Heidadouppi, Icenia, Life Ext, Melapure, Melatonin, N-(2-(5-Methoxy-1H-Indol-3-Yl)Ethyl)Acetamide, N-Acetyl-5-Methoxytryptamine, Natrol, Nature’s Blend, Natures Bounty, Quality Health, S.Gard, Travelag, Vespro, Vytalonin | 4 | 232.28 | 0.84 | Anxiety, Aortic Aneurysm, Atrial Fibrillation, Attention Deficit Disorder with Hyperactivity, Autistic Disorder, Barrett Esophagus, Brain Ischemia, Breast Neoplasms, Carcinoma, Non-Small-Cell Lung, Child Development Disorders, Pervasive, Cognitive Dysfunction, Colitis, Ulcerative, Dementia, Depressive Disorder, Dermatitis, Atopic, Diabetes Mellitus, Epilepsy, Fatigue, Fibromyalgia, Gastroesophageal Reflux, Head and Neck Neoplasms, Hemorrhage, Hypertension, Melanoma, Metabolic Diseases, Metabolic Syndrome, Migraine Disorders, Multiple Sclerosis, Relapsing-Remitting, Myocardial Infarction, Neonatal Sepsis, Neoplasms, Nocturnal Enuresis, Pain, Premature Birth, Reperfusion Injury, Schizophrenia, Sepsis, Skin Diseases, Sleep Initiation and Maintenance Disorders, Stomatitis, Substance Withdrawal Syndrome, Sunburn |
CHEMBL2103822 | TASIMELTEON | BMS-214778, Hetlioz, Tasimelteon, VEC-162 | 4 | 245.32 | 0.88 | Depressive Disorder, Liver Diseases, Sleep Initiation and Maintenance Disorders, Smith-Magenis Syndrome |
CHEMBL1218 | RAMELTEON | Ramelteon, Rozerem, TAK-375 | 4 | 259.35 | 0.9 | Bipolar Disorder, Depressive Disorder, Marijuana Abuse, Migraine with Aura, Migraine without Aura, Pulmonary Disease, Chronic Obstructive, Sleep Apnea, Obstructive, Sleep Initiation and Maintenance Disorders, Substance-Related Disorders, Tobacco Use Disorder |
CHEMBL3230568 | No Data | 0 | 246.31 | 0.87 | ||
CHEMBL3230569 | No Data | 0 | 266.73 | 0.89 | ||
CHEMBL498494 | No Data | 0 | 393.49 | 0.58 | ||
CHEMBL498493 | No Data | 0 | 393.49 | 0.58 | ||
CHEMBL525374 | No Data | 0 | 423.51 | 0.52 | ||
CHEMBL15060 | No Data | 0 | 308.38 | 0.76 | ||
CHEMBL34730 | No Data | 6-Chloromelatonin | 0 | 266.73 | 0.89 | |
CHEMBL33415 | No Data | 0 | 311.18 | 0.91 | ||
CHEMBL33700 | No Data | 0 | 246.31 | 0.89 |
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Baltatu, O.C.; Senar, S.; Campos, L.A.; Cipolla-Neto, J. Cardioprotective Melatonin: Translating from Proof-of-Concept Studies to Therapeutic Use. Int. J. Mol. Sci. 2019, 20, 4342. https://doi.org/10.3390/ijms20184342
Baltatu OC, Senar S, Campos LA, Cipolla-Neto J. Cardioprotective Melatonin: Translating from Proof-of-Concept Studies to Therapeutic Use. International Journal of Molecular Sciences. 2019; 20(18):4342. https://doi.org/10.3390/ijms20184342
Chicago/Turabian StyleBaltatu, Ovidiu Constantin, Sergio Senar, Luciana Aparecida Campos, and José Cipolla-Neto. 2019. "Cardioprotective Melatonin: Translating from Proof-of-Concept Studies to Therapeutic Use" International Journal of Molecular Sciences 20, no. 18: 4342. https://doi.org/10.3390/ijms20184342