Taltirelin

Taltirelin Hydrate Instructions

English name: Taltirelin Hydrate

Trade name: CEREDIST OD Tablets

Chinese name: Taltirelin orally disintegrating tablets

Original research company: Japan Tanabe Pharmaceutical Co., Ltd.

Drug Introduction

Taltirelin It is the world's first approved oral thyrotropin-releasing hormone (TRH). In addition to its endocrine effects, it can also exert certain central nervous system (CNS) effects, including increasing locomotor activity, antagonizing reserpine-induced hypothermia, and antagonizing pentobarbital-induced sleep. This variety was developed by Japan's Tanabe Pharmaceutical Company and launched in Japan in July 2000. It is used to improve ataxia in patients with spinocerebellar degeneration.

Pharmacological studies have shown that this product has strong and lasting multiple effects on the CNS via brain TRH receptors. The excitatory effect of this product on the CNS is 10 to 100 times stronger than that of TRH, and its duration of action is about 8 times longer than that of TRH. The affinity of this product for TRH receptor is about 1/11 of TRH, so the endocrine effect of this product is weaker than TRH, but this product is more stable than TRH in the body. In addition, the effect of this product on the release of thyroid stimulating hormone (TSH) is 1/6-1/11 of TRH.

This product has a strong effect on the central nervous system, but at the same time it has a small hormone-like effect, so it has fewer side effects. Adverse reactions are mainly digestive system reactions, including vomiting, nausea and stomach discomfort. All adverse reactions were mild to moderate and disappeared during treatment and/or after discontinuation of treatment.

セレジストOD tablets 5mg

Pharmaceutical category name

Oral spinocerebellar degeneration treatment agent

Approval date: October 2009

Trade name

CEREDIST OD Tablets 5mg

Common name

Taltirelin Hydrate

Chemical name

N-[(4S)-1-Methyl-2,6-dioxohexahydropyrimidine-4-carbonyl]-L-histidyl-L-prolinamide Tetrahydrate

Molecular formula

C17H23N7O5·4H2O

Molecular weight

477.47

Structural formula

Characteristics

It is a white crystal or crystalline powder.

Soluble in water, ethanol (99.5) or acetic acid (100), slightly soluble in methanol.

Dissolve in 1 molar hydrochloric acid measurement solution.

Polymorphisms are observed.

Medicinal Pharmacology

Ataxia-improving effect

(1) Salirin hydrate in Nagoya rolling mice, which are hereditary ataxia mice (1 mg kg, administered orally), and improved the turnover index (number of drops/spontaneous movements), increased brain glucose metabolism rate, reduced to normal levels in the ventral brainstem field (3 mg kg, administered intraperitoneally).

(2) 3-Tatirelin hydrate in ataxic rats improved ataxia (walking speed, gait length, gait angle) with acetylpyridine (qi combined with kilogram, administered orally). Note that this effect is lost by excitatory amino acid antagonists.

(3) In toxicity tests, using T, 1.5mg/kg, transient hyperactivity, seems to be based on oral administration or more efficacy, tremors and other expressions.

Neurotrophic factor-like effects

Salicylic acid is 10-12M. The neuronal progression of cultured cells on the spinal cord side of rat fetuses is promoted in a concentration-dependent manner. Postneuronal division of motor neurons in rats 2 weeks and 2 weeks old is inhibited by repeated intraperitoneal administration.

Pituitary Gland Thyroid Hormone Stimulation

Oral administration of 2.75 μmols of tartilelin hydrate - the body volume increased to 5 times that of the control group until the blood TSH of male rats 3 hours after administration. Taking TRH 0.275 μmol·body orally, the same degree of TSH-increasing effect was observed.

Mechanism of action

(1) When studying the affinity of tapirelin hydrate with various receptors and ion channels, it only showed affinity for TRH receptors.

(2) The effect of tasirelin on the free and metabolic rotation of various neurotransmitters was studied, and the intraperitoneal administration of acetylcholine and dopamine in the rat brain was sustained at 0.1mg/kg or more and 1mgkg or more, respectively. In addition, it was observed that metabolic rotation or the synthesis of neurotransmitters was also promoted.

Clinical Pharmacology

The TSH secretion-stimulating effect of a single oral dose of 0.5 to 40 mg of tasirelin was studied in healthy adults, and a dose-dependent increase in TSH concentration was observed for doses of 1 mg or more. Additionally, T3 increases significantly, at least 1 to 10 mg.

Indications

It is used to improve ataxia in patients with spinocerebellar degeneration. u3000

Usage and Dosage

Adults take 1 tablet twice a day, orally after breakfast and dinner, and can be increased or decreased appropriately according to age and symptoms

Clinical results

1. Clinical effects

For 427 cases of spinocerebellar degeneration, the results of the double-blind group comparative trial were compared with placebo administered for up to one year. Although no significant differences were recognized in various ataxia tests after 28 weeks of use, the drug was proven to be significantly better than placebo in the main evaluation items of general improvement and improvement in ataxia trials. In addition, the cumulative exacerbation rate after 28 weeks of the Kaplan-Meier method was 27.7% in the SE anti-tablet administration group and 41.7% in the placebo administration group, with significant differences. Additionally, I did not recognize a difference between the placebos until 1 year of administration (rate of deterioration) after the log-rank test of general improvement.

2. Taking [Anti-SE Tablets 5mg (normal tablets)] to the elderly (65 years old or above)

There are 96 cases of use experience over 65 years old, 14 cases (14.6%) and 18 cases of side effects. The main side effects are gastric discomfort, anorexia, dizziness, dislocation, headache, etc.

Packaging

OD tablets

5mg: 28 tablets (14 tablets x 2), 140 tablets (14 tablets x 10)