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In animals melatonin is secreted by the pineal gland during darkness [[cite:PUB00066875], [cite:PUB00066876]].  It regulates a variety of neuroendocrine functions and is thought to play an essential role in circadian rhythms [[cite:PUB00066877]].   Drugs that modify the action of melatonin, and hence influence circadian cycles, are of clinical interest for example, in the treatment of jet-lag [[cite:PUB00066878]].</p>\r\n<p>Many of the biological effects of melatonin are produced through the activation of melatonin receptors [[cite:PUB00066879]], which are members of rhodopsin-like G protein-coupled receptor family.   There are three melatonin receptor subtypes. Melatonin receptor type 1A and melatonin receptor type 1B are present in humans and other mammals [[cite:PUB00066880]] while melatonin receptor type 1C has been identified in amphibia and birds [[cite:PUB00066881]].  There is also a closely-related orphan receptor, termed melatonin-related receptor type 1X (also known as GPR50) [[cite:PUB00066882]], is yet to achieve receptor status from the International Union of Basic and Clinical Pharmacology (IUPHAR), since a robust response mediated via the protein has not been reported in the literature.  Melatonin receptor type 1C receptors are 80% identical and are distinct from 1A and 1B subtypes. Similar ligand binding and functional characteristics are observed in expressed 1A and 1C receptors.  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