用户名： 密   码：
注册 | 忘记密码？
药品详细

Riluzole(利鲁唑)

化学结构式图
中文名
利鲁唑
英文名
Riluzole
分子式
C8H5F3N2OS
化学名
6-(trifluoromethoxy)-1,3-benzothiazol-2-amine
分子量
Average: 234.198
Monoisotopic: 234.007468097
CAS号
1744-22-5
ATC分类
N07X Other Nervous System Drugs
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

A glutamate antagonist (receptors, glutamate) used as an anticonvulsant (anticonvulsants) and to prolong the survival of patients with amyotrophic lateral sclerosis. [PubChem]

生产厂家
  • Impax laboratories inc
  • Sanofi aventis us llc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Song JH, Huang CS, Nagata K, Yeh JZ, Narahashi T: Differential action of riluzole on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels. J Pharmacol Exp Ther. 1997 Aug;282(2):707-14. Pubmed
  2. Coric V, Taskiran S, Pittenger C, Wasylink S, Mathalon DH, Valentine G, Saksa J, Wu YT, Gueorguieva R, Sanacora G, Malison RT, Krystal JH: Riluzole augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial. Biol Psychiatry. 2005 Sep 1;58(5):424-8. Pubmed
  3. van Kan HJ, Groeneveld GJ, Kalmijn S, Spieksma M, van den Berg LH, Guchelaar HJ: Association between CYP1A2 activity and riluzole clearance in patients with amyotrophic lateral sclerosis. Br J Clin Pharmacol. 2005 Mar;59(3):310-3. Pubmed
  4. Zarate CA Jr, Payne JL, Quiroz J, Sporn J, Denicoff KK, Luckenbaugh D, Charney DS, Manji HK: An open-label trial of riluzole in patients with treatment-resistant major depression. Am J Psychiatry. 2004 Jan;161(1):171-4. Pubmed
  5. Mathew SJ, Manji HK, Charney DS: Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92. Epub 2008 Jan 2. Pubmed
  6. Lamanauskas N, Nistri A: Riluzole blocks persistent Na+ and Ca2+ currents and modulates release of glutamate via presynaptic NMDA receptors on neonatal rat hypoglossal motoneurons in vitro. Eur J Neurosci. 2008 May;27(10):2501-14. Epub 2008 Apr 26. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Phenols and Derivatives
  • Anisoles
  • Benzothiazoles
Substructures
  • Phenols and Derivatives
  • Aliphatic and Aryl Amines
  • Ethers
  • Halogen Derivatives
  • Benzene and Derivatives
  • Thiazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Benzothiazoles
  • Phenyl Esters
适应症
药理
Indication For the treatment of amyotrophic lateral sclerosis (ALS, Lou Gehrig's Disease)
Pharmacodynamics Riluzole, a member of the benzothiazole class, is indicated for the treatment of patients with amyotrophic lateral sclerosis (ALS). Riluzole extends survival and/or time to tracheostomy. It is also neuroprotective in various in vivo experimental models of neuronal injury involving excitotoxic mechanisms. The etiology and pathogenesis of amyotrophic lateral sclerosis (ALS) are not known, although a number of hypotheses have been advanced. One hypothesis is that motor neurons, made vulnerable through either genetic predisposition or environmental factors, are injured by glutamate. In some cases of familial ALS the enzyme superoxide dismutase has been found to be defective.
Mechanism of action The mode of action of riluzole is unknown. Its pharmacological properties include the following, some of which may be related to its effect: 1) an inhibitory effect on glutamate release (activation of glutamate reuptake), 2) inactivation of voltage-dependent sodium channels, and 3) ability to interfere with intracellular events that follow transmitter binding at excitatory amino acid receptors.
Absorption Riluzole is well-absorbed (approximately 90%), with average absolute oral bioavailability of about 60% (CV=30%). A high fat meal decreases absorption, reducing AUC by about 20% and peak blood levels by about 45%.
Volume of distribution Not Available
Protein binding 96% bound to plasma proteins, mainly to albumin and lipoprotein over the clinical concentration range.
Metabolism
Riluzole is extensively metabolized to six major and a number of minor metabolites, which have not all been identified to date. Metabolism is mostly hepatic, consisting of cytochrome P450–dependent hydroxylation and glucuronidation. CYP1A2 is the primary isozyme involved in N-hydroxylation; CYP2D6, CYP2C19, CYP3A4, and CYP2E1 are considered unlikely to contribute significantly to riluzole metabolism in humans.
Route of elimination Not Available
Half life The mean elimination half-life of riluzole is 12 hours (CV=35%) after repeated doses.
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 119 °C Not Available
logP 2.3 Not Available
Predicted Properties
Property Value Source
water solubility 3.95e-02 g/l ALOGPS
logP 2.83 ALOGPS
logP 3.4 ChemAxon
logS -3.8 ALOGPS
pKa (strongest acidic) 16.44 ChemAxon
pKa (strongest basic) 4.57 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 48.14 ChemAxon
rotatable bond count 2 ChemAxon
refractivity 44.37 ChemAxon
polarizability 18.59 ChemAxon
药物相互作用
食物相互作用
  • Take on an empty stomach 1 hour before or 2 hours after meals.

返回 | 收藏