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Central nervous system effects of thyrotropin-releasing hormone and its analogues: opportunities and perspectives for drug discovery and development

Chapter
Part of the Progress in Drug Research book series (PDR, volume 59)

Summary

Besides its well-known endocrine role in the thyroid system, thyrotropinreleasing hormone (L-pyroglutamyl-L-histidyl-L-prolinamide) has been long recognized as a modulatory neuropeptide. After a brief overview of the extrahypothalamic and receptor distribution, and of the neurophysiological, neuropharmacological and neurochemical effects of this tripeptide, this review discusses efforts devoted to enhance therapeutically beneficial central nervous system effects via structural modifications of the endogenous peptide. An enormous array of maladies affecting the brain and the spinal cord has been a potential target for therapeutic interventions involving agents derived from thyrotropin-releasing hormone as a molecular lead. Successful development of several centrally active analogues and recent accounts of efforts aimed at improving metabolic stability, selectivity and bioavailability are highlighted.

Key words

Thyrotropin-releasing hormone analogue mimetic prodrug central nervous system receptor pharmacology neurochemistry metabolism drug development neurological diseases. 

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© Springer Basel AG 2002

Authors and Affiliations

  1. 1.Center for Drug Discovery, College of Pharmacy and the McKnight Brain InstituteUniversity of Florida Health Science CenterGainesvilleUSA

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