Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

You’ve supercharged your research process with ACS and Mendeley!

STEP 1:
Click to create an ACS ID

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

MENDELEY PAIRING EXPIRED
Your Mendeley pairing has expired. Please reconnect
ACS Publications. Most Trusted. Most Cited. Most Read
My Activity
CONTENT TYPES

Design and Synthesis of Naphthalenic Dimers as Selective MT1 Melatoninergic Ligands

View Author Information
Faculté de Pharmacie, Laboratoire de Chimie Thérapeutique, Université de Lille 2, 3 Rue du Professeur Laguesse, BP 83, 59006 Lille Cedex, France, and Institut de Recherches Internationales Servier, Courbevoie Cedex, France
Cite this: J. Med. Chem. 2003, 46, 7, 1127–1129
Publication Date (Web):March 1, 2003
https://doi.org/10.1021/jm0255872
Copyright © 2003 American Chemical Society

    Article Views

    759

    Altmetric

    -

    Citations

    LEARN ABOUT THESE METRICS
    Other access options
    Supporting Info (1)»

    Abstract

    Abstract Image

    We report the synthesis and binding properties at MT1 and MT2 receptors of the first example of agomelatine (N-[2-(7-methoxynaphth-1-yl)ethyl]acetamide) dimers in which two agomelatine moieties are linked together through their methoxy substituent by a polymethylene side chain according to the “bivalent ligand” approach. Some of these compounds behave as MT1-selective ligands. The most selective one (5) behaves as an antagonist.

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. You can change your affiliated institution below.

    §

     Université de Lille 2.

    *

     To whom correspondence should be addressed:  Phone and fax:  +33(0)320964375. E-mail:  [email protected].

     Institut de Recherches Internationales Servier.

    Supporting Information Available

    ARTICLE SECTIONS
    Jump To

    Experimental section, including chemistry and pharmacology information. This material is available free of charge via the Internet at http://pubs.acs.org.

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    This article is cited by 56 publications.

    1. Darius. P. Zlotos, Ralf Jockers, Erika Cecon, Silvia Rivara, and Paula A. Witt-Enderby . MT1 and MT2 Melatonin Receptors: Ligands, Models, Oligomers, and Therapeutic Potential. Journal of Medicinal Chemistry 2014, 57 (8) , 3161-3185. https://doi.org/10.1021/jm401343c
    2. Kenneth A. Jacobson. Functionalized Congener Approach to the Design of Ligands for G Protein-Coupled Receptors (GPCRs). Bioconjugate Chemistry 2009, 20 (10) , 1816-1835. https://doi.org/10.1021/bc9000596
    3. Annalida Bedini,, Gilberto Spadoni,, Giuseppe Gatti,, Simone Lucarini,, Giorgio Tarzia,, Silvia Rivara,, Simone Lorenzi,, Alessio Lodola,, Marco Mor,, Valeria Lucini,, Marilou Pannacci, and, Francesco Scaglione. Design and Synthesis of N-(3,3-Diphenylpropenyl)alkanamides as a Novel Class of High-Affinity MT2-Selective Melatonin Receptor Ligands. Journal of Medicinal Chemistry 2006, 49 (25) , 7393-7403. https://doi.org/10.1021/jm060850a
    4. Andrew Tsotinis,, Margarita Vlachou,, Demetris P. Papahatjis,, Theodora Calogeropoulou,, Spyros P. Nikas,, Peter J. Garratt,, Vincent Piccio,, Stefan Vonhoff,, Kathryn Davidson,, Muy-Teck Teh, and, David Sugden. Mapping the Melatonin Receptor. 7. Subtype Selective Ligands Based on β-Substituted N-Acyl-5-methoxytryptamines and β-Substituted N-Acyl-5-methoxy-1-methyltryptamines. Journal of Medicinal Chemistry 2006, 49 (12) , 3509-3519. https://doi.org/10.1021/jm0512544
    5. Valeria Lucini,, Marilou Pannacci,, Francesco Scaglione,, Franco Fraschini,, Sivia Rivara,, Marco Mor,, Fabrizio Bordi,, Pier Vincenzo Plazzi,, Gilberto Spadoni,, Annalida Bedini,, Giovanni Piersanti,, Giuseppe Diamantini, and, Giorgio Tarzia. Tricyclic Alkylamides as Melatonin Receptor Ligands with Antagonist or Inverse Agonist Activity. Journal of Medicinal Chemistry 2004, 47 (17) , 4202-4212. https://doi.org/10.1021/jm040768k
    6. Annalida Bedini, Jean A. Boutin, Céline Legros, Darius P. Zlotos, Gilberto Spadoni. Industrial and academic approaches to the search for alternative melatonin receptor ligands: An historical survey. Journal of Pineal Research 2024, 76 (4) https://doi.org/10.1111/jpi.12953
    7. Yuan Gao, Shuqin Zhao, Yong Zhang, Quanwei Zhang. Melatonin Receptors: A Key Mediator in Animal Reproduction. Veterinary Sciences 2022, 9 (7) , 309. https://doi.org/10.3390/vetsci9070309
    8. Gian Marco Elisi, Laura Scalvini, Alessio Lodola, Annalida Bedini, Gilberto Spadoni, Silvia Rivara. In silico drug discovery of melatonin receptor ligands with therapeutic potential. Expert Opinion on Drug Discovery 2022, 17 (4) , 343-354. https://doi.org/10.1080/17460441.2022.2043846
    9. Jana Tchekalarova, Natasha Ivanova, Zlatina Nenchovska, Rumiana Tzoneva, Tzveta Stoyanova, Veselina Uzunova, Slavina Surcheva, Alex Tzonev, Violina T. Angelova, Pavlina Andreeva-Gateva. Evaluation of neurobiological and antioxidant effects of novel melatonin analogs in mice. Saudi Pharmaceutical Journal 2020, 28 (12) , 1566-1579. https://doi.org/10.1016/j.jsps.2020.10.004
    10. Chun-Ta Huang, Seu-Hwa Chen, Chi-Fen Chang, Shih-Chang Lin, June-Horng Lue, Yi-Ju Tsai. Melatonin reduces neuropathic pain behavior and glial activation through MT2 melatonin receptor modulation in a rat model of lysophosphatidylcholine-induced demyelination neuropathy. Neurochemistry International 2020, 140 , 104827. https://doi.org/10.1016/j.neuint.2020.104827
    11. Jean A. Boutin, Paula A. Witt‐Enderby, Christoph Sotriffer, Darius P. Zlotos. Melatonin receptor ligands: A pharmaco‐chemical perspective. Journal of Pineal Research 2020, 69 (3) https://doi.org/10.1111/jpi.12672
    12. Benjamin Stauch, Linda C. Johansson, Vadim Cherezov. Structural insights into melatonin receptors. The FEBS Journal 2020, 287 (8) , 1496-1510. https://doi.org/10.1111/febs.15128
    13. Reed M. Stein, Hye Jin Kang, John D. McCorvy, Grant C. Glatfelter, Anthony J. Jones, Tao Che, Samuel Slocum, Xi-Ping Huang, Olena Savych, Yurii S. Moroz, Benjamin Stauch, Linda C. Johansson, Vadim Cherezov, Terry Kenakin, John J. Irwin, Brian K. Shoichet, Bryan L. Roth, Margarita L. Dubocovich. Virtual discovery of melatonin receptor ligands to modulate circadian rhythms. Nature 2020, 579 (7800) , 609-614. https://doi.org/10.1038/s41586-020-2027-0
    14. Jean A. Boutin, Céline Legros. The five dimensions of receptor pharmacology exemplified by melatonin receptors: An opinion. Pharmacology Research & Perspectives 2020, 8 (1) https://doi.org/10.1002/prp2.556
    15. Erika Cecon, Lei Liu, Ralf Jockers. Melatonin receptor structures shed new light on melatonin research. Journal of Pineal Research 2019, 67 (4) https://doi.org/10.1111/jpi.12606
    16. Stefano Comai, Martha Lopez-Canul, Danilo De Gregorio, Ada Posner, Mohamed Ettaoussi, Fabrizia Claudia Guarnieri, Gabriella Gobbi. Melatonin MT1 receptor as a novel target in neuropsychopharmacology: MT1 ligands, pathophysiological and therapeutic implications, and perspectives. Pharmacological Research 2019, 144 , 343-356. https://doi.org/10.1016/j.phrs.2019.04.015
    17. Angeliki Karamitri, Mirna S. Sadek, Anne-Sophie Journé, Florence Gbahou, Romain Gerbier, Mai B. Osman, Samy A.M. Habib, Ralf Jockers, Darius P. Zlotos. O-linked melatonin dimers as bivalent ligands targeting dimeric melatonin receptors. Bioorganic Chemistry 2019, 85 , 349-356. https://doi.org/10.1016/j.bioorg.2019.01.004
    18. Preeti Jha, Shubhra Chaturvedi, Ankur Kaul, Pradeep Pant, Anju Anju, Sunil Pal, Nidhi Jain, Anil K. Mishra. Design, physico-chemical and pre-clinical evaluation of a homo-bivalent 99m Tc-(BTZ) 2 DTPA radioligand for targeting dimeric 5-HT 1A /5-HT 7 receptors. New Journal of Chemistry 2018, 42 (18) , 15032-15043. https://doi.org/10.1039/C8NJ00089A
    19. Ralf Jockers, Philippe Delagrange, Margarita L. Dubocovich, Regina P. Markus, Nicolas Renault, Gianluca Tosini, Erika Cecon, Darius P. Zlotos. Update on melatonin receptors: IUPHAR Review 20. British Journal of Pharmacology 2016, 173 (18) , 2702-2725. https://doi.org/10.1111/bph.13536
    20. Jiabei Liu, Shannon J. Clough, Anthony J. Hutchinson, Ekue B. Adamah-Biassi, Marina Popovska-Gorevski, Margarita L. Dubocovich. MT 1 and MT 2 Melatonin Receptors: A Therapeutic Perspective. Annual Review of Pharmacology and Toxicology 2016, 56 (1) , 361-383. https://doi.org/10.1146/annurev-pharmtox-010814-124742
    21. G. Viault, S. Poupart, S. Mourlevat, C. Lagaraine, S. Devavry, F. Lefoulon, V. Bozon, L. Dufourny, P. Delagrange, G. Guillaumet, F. Suzenet. Design, synthesis and biological evaluation of fluorescent ligands for MT 1 and/or MT 2 melatonin receptors. RSC Advances 2016, 6 (67) , 62508-62521. https://doi.org/10.1039/C6RA10812A
    22. Darius P. Zlotos, Noura M. Riad, Mai B. Osman, Bala R. Dodda, Paula A. Witt-Enderby. Novel difluoroacetamide analogues of agomelatine and melatonin: probing the melatonin receptors for MT 1 selectivity. MedChemComm 2015, 6 (7) , 1340-1344. https://doi.org/10.1039/C5MD00190K
    23. N. V. Kostiuk, M. B. Belyakova, D. V. Leshchenko, V. V. Zhigulina, M. V. Miniaev. Synthetic Melatoninergic Ligands: Achievements and Prospects. ISRN Biochemistry 2014, 2014 , 1-11. https://doi.org/10.1155/2014/843478
    24. Darius P. Zlotos. Development of Agonists and Antagonists for Melatonin Receptors. 2014, 97-116. https://doi.org/10.1007/978-81-322-0825-9_7
    25. Anne-Sophie Journé, Samy A. M. Habib, Bala R. Dodda, Mina N. F. Morcos, Mirna S. Sadek, Sarah A. A. Tadros, Paula A. Witt-Enderby, Ralf Jockers, Darius P. Zlotos. N1-linked melatonin dimers as bivalent ligands targeting dimeric melatonin receptors. MedChemComm 2014, 5 (6) , 792. https://doi.org/10.1039/c4md00079j
    26. King Chan, Yung Wong. A Molecular and Chemical Perspective in Defining Melatonin Receptor Subtype Selectivity. International Journal of Molecular Sciences 2013, 14 (9) , 18385-18406. https://doi.org/10.3390/ijms140918385
    27. Titiwat Sungkaworn, Chutima Jiarpinitnun, Pongkorn Chaiyakunvat, Varanuj Chatsudthipong. Bivalent angiotensin II suppresses oxidative stress-induced hyper-responsiveness of angiotensin II receptor type I. European Journal of Medicinal Chemistry 2013, 63 , 629-634. https://doi.org/10.1016/j.ejmech.2013.02.041
    28. Céline Legros, Ulrich Matthey, Teresa Grelak, Sandrine Pedragona-Moreau, Werner Hassler, Saïd Yous, Emmanuel Thomas, Franck Suzenet, Benoît Folleas, François Lefoulon, Pascal Berthelot, Daniel-Henri Caignard, Gérald Guillaumet, Philippe Delagrange, Jean-Louis Brayer, Olivier Nosjean, Jean Boutin. New Radioligands for Describing the Molecular Pharmacology of MT1 and MT2 Melatonin Receptors. International Journal of Molecular Sciences 2013, 14 (5) , 8948-8962. https://doi.org/10.3390/ijms14058948
    29. Marouan Rami, Elodie Landagaray, Mohamed Ettaoussi, Koussayla Boukhalfa, Daniel-Henri Caignard, Philippe Delagrange, Pascal Berthelot, Saïd Yous. Novel Conformationally Constrained Analogues of Agomelatine as New Melatoninergic Ligands. Molecules 2013, 18 (1) , 154-166. https://doi.org/10.3390/molecules18010154
    30. Silvia Rivara, Daniele Pala, Alessio Lodola, Marco Mor, Valeria Lucini, Silvana Dugnani, Francesco Scaglione, Annalida Bedini, Simone Lucarini, Giorgio Tarzia, Gilberto Spadoni. MT 1 ‐Selective Melatonin Receptor Ligands: Synthesis, Pharmacological Evaluation, and Molecular Dynamics Investigation of N ‐{[(3‐ O ‐Substituted)anilino]alkyl}amides. ChemMedChem 2012, 7 (11) , 1954-1964. https://doi.org/10.1002/cmdc.201200303
    31. Konstantin Yuryevich Koltunov, Aleksey Nikolaevich Chernov, Gubbi Krishnamurthy Surya Prakash, George Andrew Olah. Condensation of 2-Naphthol and Naphthalenediols with o-Dichlorobenzene in the Presence of Aluminum Halides. Chemical and Pharmaceutical Bulletin 2012, 60 (6) , 722-727. https://doi.org/10.1248/cpb.60.722
    32. Gilberto Spadoni, Annalida Bedini, Silvia Rivara, Marco Mor. Melatonin Receptor Agonists: New Options for Insomnia and Depression Treatment. CNS Neuroscience & Therapeutics 2011, 17 (6) , 733-741. https://doi.org/10.1111/j.1755-5949.2010.00197.x
    33. Christian Markl, William P. Clafshenkel, Mohamed I. Attia, Shalini Sethi, Paula A. Witt‐Enderby, Darius P. Zlotos. N ‐Acetyl‐5‐arylalkoxytryptamine Analogs: Probing the Melatonin Receptors for MT 1 ‐Selectivity. Archiv der Pharmazie 2011, 344 (10) , 666-674. https://doi.org/10.1002/ardp.201100125
    34. Gilberto Spadoni, Annalida Bedini, Pierfrancesco Orlando, Simone Lucarini, Giorgio Tarzia, Marco Mor, Silvia Rivara, Valeria Lucini, Marilou Pannacci, Francesco Scaglione. Bivalent ligand approach on N-{2-[(3-methoxyphenyl)methylamino]ethyl}acetamide: Synthesis, binding affinity and intrinsic activity for MT1 and MT2 melatonin receptors. Bioorganic & Medicinal Chemistry 2011, 19 (16) , 4910-4916. https://doi.org/10.1016/j.bmc.2011.06.063
    35. Christophe Mésangeau, Mikaël Fraise, Philippe Delagrange, Daniel Henri Caignard, Jean Albert Boutin, Pascal Berthelot, Saïd Yous. Preparation and pharmacological evaluation of a novel series of 2-(phenylthio)benzo[b]thiophenes as selective MT2 receptor ligands. European Journal of Medicinal Chemistry 2011, 46 (5) , 1835-1840. https://doi.org/10.1016/j.ejmech.2011.02.044
    36. Margarita L. Dubocovich, Philippe Delagrange, Diana N. Krause, David Sugden, Daniel P. Cardinali, James Olcese. International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, Classification, and Pharmacology of G Protein-Coupled Melatonin Receptors. Pharmacological Reviews 2010, 62 (3) , 343-380. https://doi.org/10.1124/pr.110.002832
    37. Christophe Mésangeau, Basile Pérès, Carole Descamps-François, Philippe Chavatte, Valérie Audinot, Sophie Coumailleau, Jean A. Boutin, Philippe Delagrange, Caroline Bennejean, Pierre Renard, Daniel H. Caignard, Pascal Berthelot, Saïd Yous. Design, synthesis and pharmacological evaluation of novel naphthalenic derivatives as selective MT1 melatoninergic ligands. Bioorganic & Medicinal Chemistry 2010, 18 (10) , 3426-3436. https://doi.org/10.1016/j.bmc.2010.04.008
    38. Sophie Poissonnier-Durieux, Mohamed Ettaoussi, Basile Pérès, Jean A. Boutin, Valérie Audinot, Caroline Bennejean, Philippe Delagrange, Daniel Henri Caignard, Pierre Renard, Pascal Berthelot, Daniel Lesieur, Saïd Yous. Synthesis of 3-phenylnaphthalenic derivatives as new selective MT2 melatoninergic ligands. Bioorganic & Medicinal Chemistry 2008, 16 (18) , 8339-8348. https://doi.org/10.1016/j.bmc.2008.08.052
    39. Konstantin Yu. Koltunov. Condensation of naphthalenediols with benzene in the presence of aluminum bromide: an efficient synthesis of 5-, 6-, and 7-hydroxy-4-phenyl-1- and 2-tetralones. Tetrahedron Letters 2008, 49 (24) , 3891-3894. https://doi.org/10.1016/j.tetlet.2008.04.062
    40. Valérie Audinot, Anne Bonnaud, Line Grandcolas, Marianne Rodriguez, Nadine Nagel, Jean-Pierre Galizzi, Ales Balik, Sophie Messager, David G. Hazlerigg, Perry Barrett, Philippe Delagrange, Jean A. Boutin. Molecular cloning and pharmacological characterization of rat melatonin MT1 and MT2 receptors. Biochemical Pharmacology 2008, 75 (10) , 2007-2019. https://doi.org/10.1016/j.bcp.2008.02.022
    41. Jean-Marie Contreras, Wolfgang Sippl. Homo and Heterodimer Ligands: the Twin Drug Approach. 2008, 380-414. https://doi.org/10.1016/B978-0-12-374194-3.00018-4
    42. Margarita L. Dubocovich. Melatonin receptors: Role on sleep and circadian rhythm regulation. Sleep Medicine 2007, 8 , 34-42. https://doi.org/10.1016/j.sleep.2007.10.007
    43. Marcello Leopoldo, Enza Lacivita, Nicola A. Colabufo, Mauro Niso, Francesco Berardi, Roberto Perrone. Bivalent ligand approach on 4-[2-(3-methoxyphenyl)ethyl]-1-(2-methoxyphenyl)piperazine: Synthesis and binding affinities for 5-HT7 and 5-HT1A receptors. Bioorganic & Medicinal Chemistry 2007, 15 (15) , 5316-5321. https://doi.org/10.1016/j.bmc.2007.05.010
    44. Pei‐Wen Wu, Yi‐Ming Cheng, Wan‐Ting Hsieh, Yu‐Hsiu Wang, Ching‐Yen Wei, Pi‐Tai Chou. 7‐Azamelatonin: Efficient Synthetic Routes, Excited‐State Double Proton Transfer Properties and Biomedical Implications. ChemMedChem 2007, 2 (7) , 1071-1075. https://doi.org/10.1002/cmdc.200700043
    45. Barbara Di Giacomo, Annalida Bedini, Gilberto Spadoni, Giorgio Tarzia, Franco Fraschini, Marilou Pannacci, Valeria Lucini. Synthesis and biological activity of new melatonin dimeric derivatives. Bioorganic & Medicinal Chemistry 2007, 15 (13) , 4643-4650. https://doi.org/10.1016/j.bmc.2007.03.080
    46. Rüdiger Faust, Peter J. Garratt, Maria Angeles Trujillo Pérez, Vincent J.-D. Piccio, Christian Madsen, Ane Stenstrøm, Bente Frølund, Kathryn Davidson, Muy-Teck Teh, David Sugden. 7-Substituted-melatonin and 7-substituted-1-methylmelatonin analogues: Effect of substituents on potency and binding affinity. Bioorganic & Medicinal Chemistry 2007, 15 (13) , 4543-4551. https://doi.org/10.1016/j.bmc.2007.04.013
    47. Margarita L. Dubocovich. Melatonin Receptors in Central Nervous System. 2007https://doi.org/10.1002/9780470101001.hcn047
    48. Alexander Greer, Orrette R. Wauchope, Nicola S. Farina, Paul Haberfield, Joel F. Liebman. Paradigms and paradoxes: Mechanisms for possible enhanced biological activity of bilaterally symmetrical chemicals. Structural Chemistry 2006, 17 (4) , 347-350. https://doi.org/10.1007/s11224-006-9008-2
    49. Jean A. Boutin, Valérie Audinot, Gilles Ferry, Philippe Delagrange. Molecular tools to study melatonin pathways and actions. Trends in Pharmacological Sciences 2005, 26 (8) , 412-419. https://doi.org/10.1016/j.tips.2005.06.006
    50. Darius P. Zlotos. Recent Advances in Melatonin Receptor Ligands. Archiv der Pharmazie 2005, 338 (5-6) , 229-247. https://doi.org/10.1002/ardp.200400996
    51. George N. Karageorge, Stephen Bertenshaw, Lawrence Iben, Cen Xu, Nathan Sarbin, Anthony Gentile, Gene M. Dubowchik. Tetrahydroisoquinoline derivatives as melatonin MT2 receptor antagonists. Bioorganic & Medicinal Chemistry Letters 2004, 14 (23) , 5881-5884. https://doi.org/10.1016/j.bmcl.2004.09.024
    52. Li-Qiang Sun, Jie Chen, Marc Bruce, Jeffrey A Deskus, James R Epperson, Katherine Takaki, Graham Johnson, Lawrence Iben, Cathy D Mahle, Elaine Ryan, Cen Xu. Synthesis and structure–activity relationship of novel benzoxazole derivatives as melatonin receptor agonists. Bioorganic & Medicinal Chemistry Letters 2004, 14 (14) , 3799-3802. https://doi.org/10.1016/j.bmcl.2004.04.082
    53. Carlos Larraya, Jérôme Guillard, Pierre Renard, Valérie Audinot, Jean A Boutin, Philippe Delagrange, Caroline Bennejean, Marie-Claude Viaud-Massuard. Preparation of 4-azaindole and 7-azaindole dimers with a bisalkoxyalkyl spacer in order to preferentially target melatonin MT1 receptors over melatonin MT2 receptors. European Journal of Medicinal Chemistry 2004, 39 (6) , 515-526. https://doi.org/10.1016/j.ejmech.2004.03.005
    54. J. Barrenetxe, P. Delagrange, J. A. Martínez. Physiological and metabolic functions of melatonin. Journal of Physiology and Biochemistry 2004, 60 (1) , 61-72. https://doi.org/10.1007/BF03168221
    55. Li-Qiang Sun, Jie Chen, Katherine Takaki, Graham Johnson, Lawrence Iben, Cathy D. Mahle, Elaine Ryan, Cen Xu. Design and synthesis of benzoxazole derivatives as novel melatoninergic ligands. Bioorganic & Medicinal Chemistry Letters 2004, 14 (5) , 1197-1200. https://doi.org/10.1016/j.bmcl.2003.12.052
    56. Laura R. Fitzgerald, Jessica E. Reed. Melatonin Agonists for the Treatment of Sleep Disorders and Major Depression. 2004, 25-37. https://doi.org/10.1016/S0065-7743(04)39003-2