Droxidopa

Các tên gọi khác (4 ) :

Dops
L-Dihydroxyphenylserine
L-DOPS
L-threo-dihydroxyphenylserine

Thuốc chống Parkinson

Thuốc Gốc

Small Molecule

CAS: 23651-95-8

CTHH: C₉H₁₁NO₅

PTK: 213.1873

Droxidopa is a precursor of noradrenaline that is used in the treatment of Parkinsonism. It is approved for use in Japan and is currently in trials in the U.S. The racaemic form (dl-threo-3,4-dihydroxyphenylserine) has also been used, and has been investigated in the treatment of orthostatic hypotension. There is a deficit of noradrenaline as well as of dopamine in Parkinson's disease and it has been proposed that this underlies the sudden transient freezing seen usually in advanced disease. Though L-DOPS has been used in Japan and Southeast Asia already for some time, it is also currently in clinical trials at the phase III point in the United States (U.S.), Canada, Australia, and throughout Europe. Provided L-DOPS successfully completes clinical trials, it could be approved for the treatment of neurogenic orthostatic hypotension (NOH) as early as 2011. Additionally, phase II clinical trials for intradialytic hypotension are also underway. Chelsea Therapeutics obtained orphan drug status (ODS) for L-DOPS in the U.S. for NOH, and that of which associated with Parkinson's disease , pure autonomic failure, and multiple system atrophy, and is the pharmaceutical company developing it in that country.

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₉H₁₁NO₅

Phân tử khối

213.1873

Monoisotopic mass

213.063722467

InChI

InChI=1S/C9H11NO5/c10-7(9(14)15)8(13)4-1-2-5(11)6(12)3-4/h1-3,7-8,11-13H,10H2,(H,14,15)/t7-,8+/m1/s1

InChI Key

InChIKey=QXWYKJLNLSIPIN-SFYZADRCSA-N

IUPAC Name

(2R,3S)-2-amino-3-(3,4-dihydroxyphenyl)-3-hydroxypropanoic acid

Traditional IUPAC Name

droxidopa

SMILES

N[C@H]([C@@H](O)C1=CC(O)=C(O)C=C1)C(O)=O

Độ hòa tan

1.53e+01 g/l

logP

-2.7

logS

-1.1

pKa (strongest acidic)

1.46

pKa (Strongest Basic)

8.72

PSA

124.01 Å²

Refractivity

50.29 m³·mol^-1

Polarizability

19.63 Å³

Rotatable Bond Count

H Bond Acceptor Count

H Bond Donor Count

Physiological Charge

Number of Rings

Bioavailability

Rule of Five

true

Dược Lực Học : Droxidopa is an orally active synthetic precursor of norepinephrine that increases the deficient supply of norepinephrine in patients with NOH, thereby improving orthostatic blood pressure and alleviating associated symptoms of lightheadedness, dizziness, blurred vision, and syncope through the induction of tachycardia (increased heart rate) and hypertension.

Cơ Chế Tác Dụng : Droxidopa is a precursor of noradrenaline that is used in the treatment of Parkinsonism. It is approved for use in Japan and is currently in trials in the U.S. The racaemic form (dl-threo-3,4-dihydroxyphenylserine) has also been used, and has been investigated in the treatment of orthostatic hypotension. There is a deficit of noradrenaline as well as of dopamine in Parkinson's disease and it has been proposed that this underlies the sudden transient freezing seen usually in advanced disease. Though L-DOPS has been used in Japan and Southeast Asia already for some time, it is also currently in clinical trials at the phase III point in the United States (U.S.), Canada, Australia, and throughout Europe. Provided L-DOPS successfully completes clinical trials, it could be approved for the treatment of neurogenic orthostatic hypotension (NOH) as early as 2011. Additionally, phase II clinical trials for intradialytic hypotension are also underway. Chelsea Therapeutics obtained orphan drug status (ODS) for L-DOPS in the U.S. for NOH, and that of which associated with Parkinson's disease , pure autonomic failure, and multiple system atrophy, and is the pharmaceutical company developing it in that country. Droxidopa crosses the blood-brain barrier where it is converted to norepinephrine via decarboxylation by L-aromatic-amino-acid decarboxylase. Increased levels of norepinephrine in the central nervous system (CNS) may be beneficial to patients in a wide range of indications. Norephinephrine acts at alpha-adrenergic receptors as a vasoconstrictor and at beta-adrenergic receptors as a heart stimulator and artery dilator.

Dược Động Học :

▧ Absorption :
Oral bioavailability is 90%.
▧ Metabolism :
Droxidopa is metabolized by aromatic L-amino acid decarboxylase.
▧ Route of Elimination :
Droxidopa is mainly excreted in the urine, with the main metabolite being 3-O-methyldihydroxyphenylserine.
▧ Half Life :
2-3 hours.

Độc Tính : Droxidopa has minimal toxic effects and an acute, oral LD50 of more than 5 g/kg in mice, rats, dogs, and monkeys. Side effects occur in in 0.78% of patients and include nausea, headache, increased blood pressure, hallucination, and anorexia.

Chỉ Định : For treatment of neurogenic orthostatic hypotension (NOH) associated with various disorders including Multiple System Atrophy, Familial Amyloid Polyneuropathy, hemodialysis induced hypotension and Parkinson's Disease. Also investigated for use/treatment in neurologic disorders, nephropathy, blood (blood forming organ disorders, unspecified), and dizzy/fainting spells.

Liều Lượng & Cách Dùng : Tablet - Oral

Dữ Kiện Thương Mại

Nhà Sản Xuất

Công ty :

Sản phẩm biệt dược : Dops
Công ty :

Sản phẩm biệt dược : Northera

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB06262

PubChem Compound

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=443940

PubChem Substance

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=99443239

KEGG Drug

http://www.genome.jp/dbget-bin/www_bget?drug:D01277

ChemSpider

http://www.chemspider.com/Chemical-Structure.391994.html

National Drug Code Directory

http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/76320-100

PharmGKB

http://www.pharmgkb.org/drug/PA164748386

Wikipedia

http://en.wikipedia.org/wiki/Droxidopa

Bạn thấy hài lòng ?

Bạn chưa hài lòng ?

... loading