[Synthesis and pharmacological action of TRH analog peptide (Taltirelin)]

Nihon Yakurigaku Zasshi. 1997 Oct:110 Suppl 1:33P-38P. doi: 10.1254/fpj.110.supplement_33.
[Article in Japanese]

Abstract

Taltirelin hydrate[1-methyl-(S)-4,5-dihydroorotyl-L-histidyl-L-prolineamide tetrahydrate] is a new orally active thyrotropin releasing hormone (TRH) peptide analog synthetized from aspartic acid. From preclinical studies with mice and rats, Taltirelin hydrate was found to be highly stable in the blood and brain as compared with TRH. Furthermore, the CNS stimulating actions of Taltirelin hydrate such as antagonistic actions against pentobarbital-induced anesthesia and reserpine- induced hypothermia were found to be about 100 times stronger and about 8 times longer-lasting as compared with those of TRH. Meanwhile, the affinity of Taltirelin hydrate for TRH-receptors was about 10 times lower, and the endocrine action was about 5 times less potent than those of TRH. Therefore, high CNS-selectivity and long-lasting action of Taltirelin hydrate would be attributed to its high stability in the body and low affinity for TRH-receptors. Oral administrations of Taltirelin hydrate ameliorated consiousness impairment, memory impairment and motor dysfunction in several models. The clinical studies for patients with spinocerebellar degeneration are in progress.

Publication types

  • English Abstract
  • Review

MeSH terms

  • Animals
  • Aspartic Acid
  • Drug Stability
  • Humans
  • Mice
  • Nootropic Agents / chemical synthesis*
  • Nootropic Agents / pharmacokinetics
  • Nootropic Agents / pharmacology
  • Pentobarbital / antagonists & inhibitors
  • Rats
  • Receptors, Thyrotropin-Releasing Hormone / metabolism
  • Reserpine / antagonists & inhibitors
  • Thyrotropin-Releasing Hormone / analogs & derivatives*
  • Thyrotropin-Releasing Hormone / chemical synthesis
  • Thyrotropin-Releasing Hormone / pharmacokinetics
  • Thyrotropin-Releasing Hormone / pharmacology

Substances

  • Nootropic Agents
  • Receptors, Thyrotropin-Releasing Hormone
  • TA 0910
  • Aspartic Acid
  • Thyrotropin-Releasing Hormone
  • Reserpine
  • Pentobarbital