Taltirelin acetate

Taltirelin acetate (CAS No.: 1549593-23-8) is the acetate form of Taltirelin (CAS No.: 103300-74-9). As a long-acting oral analog of thyrotropin-releasing hormone (TRH, CAS No.: 24305-27-9, Catalog No.: BA7510), Taltirelin’s core biological functions rely on the specific activation of TRH Receptor 1 (TRHR1). Meanwhile, it can regulate the functions of vesicular monoamine transporter 2 (VMAT2), dopamine transporter (DAT), and tyrosine hydroxylase (TH), exerting effects by inhibiting monoamine oxidase-B (MAO-B) activity, reducing oxidative stress and apoptosis, and blocking asparagine endopeptidase (AEP)-mediated pathological cleavage of tau/α-synuclein.

In animal experiments, this drug is mainly used in therapeutic model studies, including 6-hydroxydopamine (6-OHDA)-lesioned, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced, and rotenone-induced Parkinson’s disease (PD) models, chloroquine-induced acute itch models, diphenylcyclopropenone-induced chronic itch models, as well as rat models related to obstructive sleep apnea (OSA). Additionally, it is employed in the bioequivalence evaluation of orally disintegrating tablets and immediate-release formulations in Biopharmaceutical Classification System (BCS)-based biowaiver studies.

At the cellular level, a concentration of 5 μM is commonly used in neurotoxicity resistance experiments on SH-SY5Y cells, rat primary midbrain neurons, and striatal neurons. For in vivo administration in animals, a dose of 1-10 mg/kg via intraperitoneal injection is frequently used in PD models; 1.0-3.0 mg/kg via intraperitoneal injection shows significant efficacy in itch models; in OSA studies, the local microperfusion concentration ranges from 0.1-10 μM, and the common systemic dosage is 1 mg/kg via intraperitoneal injection. Clinically, Taltirelin has been approved for the treatment of spinocerebellar degeneration (SCD), and long-term oral administration of 2.5-20 mg has no significant impact on the hypothalamic-pituitary-thyroid axis.

References:

[1] Ono A, Sugano K. Application of the BCS biowaiver approach to assessing bioequivalence of orally disintegrating tablets with immediate release formulations. Eur J Pharm Sci. 2014 Nov 20;64:37-43. doi: 10.1016/j.ejps.2014.08.003. Epub 2014 Aug 23. PMID: 25151946.

[2] Zheng C, Chen G, Tan Y, Zeng W, Peng Q, Wang J, Cheng C, Yang X, Nie S, Xu Y, Zhang Z, Papa SM, Ye K, Cao X. TRH Analog, Taltirelin Improves Motor Function of Hemi-PD Rats Without Inducing Dyskinesia via Sustained Dopamine Stimulating Effect. Front Cell Neurosci. 2018 Nov 13;12:417. doi: 10.3389/fncel.2018.00417. PMID: 30555300; PMCID: PMC6282053.

[3] Zheng C, Chen G, Tan Y, Zeng W, Peng Q, Wang J, Cheng C, Yang X, Nie S, Xu Y, Zhang Z, Papa SM, Ye K, Cao X. TRH Analog, Taltirelin Protects Dopaminergic Neurons From Neurotoxicity of MPTP and Rotenone. Front Cell Neurosci. 2018 Dec 20;12:485. doi: 10.3389/fncel.2018.00485. PMID: 30618632; PMCID: PMC6306470.

[4] Eto K, Ogata M, Kojima F, Ishibashi H. Thyrotropin-Releasing Hormone Analog Taltirelin Inhibits Acute and Chronic Itch in Mice. Biol Pharm Bull. 2024;47(11):1927-1930. doi: 10.1248/bpb.b24-00449. PMID: 39603612.

[5] Zhu K, Meng L, Luo J, Wen T, Dan L, Wang Z, Cao X, Zhang Z, Chen G. Taltirelin induces TH expression by regulating TRHR and RARα in medium spiny neurons. J Transl Med. 2024 Dec 30;22(1):1158. doi: 10.1186/s12967-024-06020-x. PMID: 39736794; PMCID: PMC11687129.