Taltirelin is a thyrotropin-releasing hormone (TRH) analog that binds the brain BRH receptors in vivo. Taltirelin has resistance to the enzymatic degradation. Multiple mechanisms for the neuroprotective effect of TRH have been proposed. These mechanisms include enhancing brain metabolism of bioamine, improving brain blood flow, ion homeostasis and improving cellular bioenergy status. But the TRH analogue taltirelin has pharmacological effects on the central nervous system, and its effectiveness lasts longer than TRH.
Pharmacological studies have shown that taltirelin produces strong and long-lasting multiple effects on the central nervous system (CNS) via the brain TRH receptor. Taltirelin's excitatory effect on CNS is 10 to 100 times stronger than TRH, and its duration is about 8 times longer than TRH. Taltirelin has an affinity for the TRH receptor of about 1/11 of TRH, and thus the endocrine effect of taltirelin is weaker than TRH. But taltirelin is more stable in vivo than TRH. In addition, the effect of taltirelin on the release of thyroid stimulating hormone (TSH) is 1/6 -1/11 of TRH. The release of TSH is regulated by a strong negative feedback system that includes thyroid hormones. This negative feedback system also inhibits the potential endocrine effects of taltirelin.
After injection of taltirelin, the Kd value of specific [3H]MeTRH binding increased significantly, and had little effect on Bmax value. These data indicate that taltirelin may significantly occupy TRH receptor sites in the ischemic brain as well as in the sham tissue under in vivo conditions. An increase in receptor binding affinity to Terreline may occur in the ischemic brain.
Pharmacokinetics and metabolism
Taltirelin is absorbed by the small intestine after oral administration. Healthy adult male volunteers orally took 0.5-40 mg of taltirelin once and reached peak plasma levels in about 3 to 5 hours.Food can reduce the absorption of this product by about 25 % and reduce the plasma concentration of the drug. The metabolism of taltirelin is similar to that of TRH, which is mainly excreted in the urine by the kidneys and has a half-life of about 2 to 4 hours. No drug accumulation was observed in repeated administration.
1. Akihiko Urayama, Shizuo Yamada, Ryohei Kimura, Jun Zhang, Yasuo Watanabe. Neuroprotective effect and brain receptor binding of taltirelin, a novel thyrotropin-releasing hormone (TRH) analogue, in transient forebrain ischemia of C57BL/6J mice. Life Sciences Volume 72, Issues 4–5, 20 December 2002, Pages 601-607
2. A.I. FadenPharmacological treatment of central nervous system trauma. Pharmacology and Toxicology, 78 (1) (1996), pp. 12-17