350 rub
Journal №5 for 2011 г.
Article in number:
Melatonin Receptors and Their Agonists
Keywords: Melatonin melatonin receptors and binding sites agonists of melatonin receptors
Authors:
N.V. Kostiuk, V.V. Zhigulina, M.B. Belyakova, D.V. Leschenko, M.V. Minyaev
Abstract:
In recent decades the pineal hormone melatonin is used in the treatment of circadian rhythms disorders, in the therapy of cardiovascular, oncological, and other diseases. However, the short half-life period and the multiplicity of biological effects of the hormone require to find new, more metabolically stable, melatoninergic agonists. Advances in this direction came possible due to the study of biochemical and molecular biological mechanisms of melatonin action, in particular, the discovery of its numerous receptors and binding sites. In the present, it was found a several groups of molecules which pretend to the role of melatonin receptors. The greatest certainty achieved for the membrane (МТ1 and МТ2) and nuclear (RZR/ROR and RZR/ROR) receptors. Discussion concerning other binding sites of melatonin (МТ3, GPR50), is far from complete. Large-scale search for efficient agonists of melatonin receptors was launched in the late 80's. To date a great number of structurally different compounds were tested. Effective agonists were found among indole derivatives, benzoxazole, benzofuran, naphthalene, tetralin. Highly selective ligands of specific melatonin receptors were discovered. Among many of studied compounds only agonists of membranous melatonin receptors present a clinical interest. Tasimelteon, ramelteon and -methyl-6-chloromelatonin are potential drugs for the treatment of primary insomnia and restoration of disturbed circadian rhythms. Agomelatine is not only an agonist of МТ1, МТ2, but also a weak antagonist of serotonin 5-HT2С receptors, thus can be used for the treatment of depressive disorders. 2-Bromomelatonin has an analgesic effect comparable to propofol. Although information about pharmacokinetic features of the melatoninergic agonists have not yet disclosed, the available data suggest that new drugs circulate in the blood for a longer time than the natural hormone. Most of these drugs are in late stages of clinical trials or undergo licensing procedures and soon may appear on the pharmaceutical market.
Pages: 49-59
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