Novel thyrotropin-releasing hormone analogs: a patent review.
BACKGROUND
The potential therapeutic applications of thyrotropin-releasing hormone (TRH) have attracted attention, based on its broad-spectrum neuropharmacological action rather than its endocrine properties. These central nervous system (CNS)-mediated effects provide the rationale for use of TRH and its analogs in the treatment of brain and spinal injury, and CNS disorders like schizophrenia, Alzheimer's disease, epilepsy, amyotrophic lateral sclerosis, Parkinson's disease, depression, shock and ischemia.


METHODS
This review summarizes the patent literature and advances in the discovery and development of novel TRH analogs over the past 20 years. It provides a comprehensive overview of the development of new TRH analogs, giving emphasis to their pharmaceutical profile.


CONCLUSIONS
The use of TRH in the treatment of various CNS disorders has been proven clinically. However, TRH itself is a poor drug candidate due to its short plasma half-life (5 min), poor biopharmaceutical properties (low intestinal and CNS permeability) and endocrine side effect. Nevertheless, researchers have come up with metabolically stable, more potent and selective TRH analogs and prodrugs. Taltirelin, one of the TRH analogs, has been approved under the trade name of Ceredist(®) in Japan for the treatment of spinocerebellar degeneration. Several other TRH analogs are in various stages of preclinical or clinical development.
National Institute of Pharmaceutical Education and Research (NIPER), Department of Pharmaceutics, Mohali, Punjab, India.
Kailas S
KS
Khomane
Chhuttan L
CL
Meena
Rahul
R
Jain
Arvind K
AK
Bansal
D000818:Animals; D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000503:physiopathology; D015195:Drug Design; D006207:Half-Life; D006801:Humans; D010330:Patents as Topic; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000187:drug effects / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology*; D014018:Tissue Distribution
D018025:Receptors, Thyrotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone