Thyrotropin-releasing hormone (TRH) is a neuropeptide having many biological and pharmacological activities. TRH (protirelin tartrate) has been used for the treatment of persistent disturbance of consciousness disorder because of its amelioratory effect. However, therapeutic use of TRH entails problems, such as its low lipophilicity, short half-life times due to specific degradation enzymes, and low penetration of the blood-brain barrier (BBB) for access to the central nervous system (CNS). To overcome such problems, a large number of TRH mimetics have been developed for the treatment of various neurological and psychiatric disorders, including spinocerebellar degeneration (SCD), cognitive impairment, and Alzheimer’s disease (AD), given by non-oral routes such as intravenous (iv) administration. However, orally effective TRH mimetics are needed to help improve the quality of life (QOL) of patients. As the first orally active TRH mimetic for the treatment of SCD, Taltirelin (Ceredist) has been launched in Japan for administration twice a day. Recently, rovatirelin reported to have high oral bioavailability (BA), was developed for SCD as a potentially effective treatment option in clinical trials by oral administration once a day. This would allow treatment with TRH and its mimetics to be moved from the hospital to outpatient or homecare facilities, and their use for a wider range of disorders. In the near future, TRH and its mimetics should become available as one of the key treatments for various neurological and psychiatric conditions, such as AD, Parkinson’s disease (PD), depression and so on.
Keywords: Alzheimer’s disease, Amyotrophic lateral sclerosis, Bioavailability, Blood-brain barrier, Central nervous system effect, Clinical trials, Depression, Drug delivery system, Endocrine effect, Epilepsy, Lipophilicity, Mimetic, Orally effective, Pain, Parkinson’s disease, Peptide, Sleep disorder, Specific degradation enzyme, Spinocerebellar degeneration, Thyrotropin-releasing hormone.