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Chemistry and Biology of Thyrotropin-Releasing Hormone (TRH) and its Analogs

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Thyrotropin-releasing hormone (TRH), a hypothalamic orally active neuropeptide, has been manifested in a wide range of biological responses. Besides its central role in regulating the pituitary-thyroid axis by simulating the release of thyrotropin, TRH has considerable influence on the activity of a number of neurobiological systems. Due to the therapeutic potential of TRH to treat several CNS maladies, the development of CNS-selective and metabolically stable TRH analogs is an area of interest. TRH is known to elicit its biological response through two G-protein coupled receptors for TRH (namely, TRH-R1 and TRH-R2). The distinct distribution of TRH receptors in tissues has provided opportunity to discover receptor subtype-specific analogs, which would demonstrate high CNS activities, and are completely free of hormonal activities. In this review, an in-depth analysis of the chemistry and biology of TRH and its analogs is provided. Recent discoveries of TRH-R2 selective analogs, TRH super agonists, metabolically stable TRH analogs, and targeted delivery of TRH analogs have been also discussed.
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Keywords: CNS; Peptide; hormone; pituitary; receptors

Document Type: Research Article

Affiliations: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, Punjab 160 062, India.

Publication date: 2008-11-01

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