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20-September-2008 09:55:50 - Droxidopa Droxidopa Systematic IUPAC name 2R,3S-2-amino-3-3,4-dihydroxyphenyl-3-hydroxypropanoic acid Identifiers CAS number 23651-95-8 ATC code ? PubChem 3171 Chemical data Formula C9H11NO5 Mol. mass 213.18734 g/mol Pharmacokinetic data Bioavailability 90% Metabolism hepatic Half life 2-3 hours Excretion renal Therapeutic considerations Pregnancy cat. ? Legal status Rx-only not yet approved in the US Routes Oral Droxidopa L-threo DOPS, L-DOPS is a synthetic amino acid precursor of the neurotransmitter and hormone norepinephrine noradrenalin. Contents 1 History 2 Therapeutic Use 3 Potential Indications 4 Adverse Effects 5 Clinical Trials 6 References 7 External Links History Droxidopa was developed by Sumitomo Pharmaceuticals for treatment of neurogenic orthostatic hypotension associated with various disorders including Multiple System Atrophy, Familial Amyloid Polyneuropathy, hemodialysis induced hypotension and Parkinson's Disease . The drug has been approved in Japan in these indications since 1989. Following a merger with Dainippon Pharmaceuticals in 2006, Dainippon Sumitomo Pharma licensed the drug to Chelsea Therapeutics to develop and market the drug worldwide except in Japan, Korea, China and Taiwan. Chelsea obtained Orphan Drug Status for droxidopa in the US for symptomatic neurogenic orthostatic hypotension associated with Parkinson's Disease, Pure Autonomic Failure and Multiple System Atrophy and is currently in phase III trials. Therapeutic Use Droxidopa is a prodrug of norepinephrine used to increase the levels of norepinephrine in the body. It is metabolized by aromatic L-amino acid decarboxylase. Patients with neurogenic orthostatic hypotension have depleted levels of norepinephrine which leads to decreased blood pressure upon orthostatic challenge.1 Droxidopa works by increasing the levels of peripheral norepinephrine thus enabling the body to maintain blood pressure during standing. Droxidopa can also cross the blood-brain barrier where it is converted to norepinephrine.2 Increased levels of norepinephrine in the central nervous system CNS may be beneficial to patients in a wide range of indications. Droxidopa can be coupled with a peripheral DOPA decarboxylase inhibitor Carbidopa or benserazide to increase CNS norepinephrine levels while maintaining peripheral levels. Potential Indications Neurogenic orthostatic hypotension Intradialytic hypotension IDH Hypotension associated with Fibromyalgia and Chronic Fatigue Syndrome3 Adverse Effects With close to 20 years on the market, droxidopa has proven to have very few side effects of which most are mild. Patients have reported increased blood pressure, nausea and headache.4 Clinical Trials Droxidopa is currently being studied in phase III trials in the US, Canada, Australia and throughout Europe. Provided successful completion of the trials, droxidopa could be approved for the symptomatic neurogenic orthostatic hypotension indication in 2009.5 A phase II trial in IDH is also underway. References ^ Robertson, David 2008. The pathophysiology and diagnosis of orthostatic hypotension. Clin Auton Res 18 Supplement 1: 2-7. ^ Goldstein, DS 2006. L-Dihydroxyphenylserine L-DOPS: a norepinephrine prodrug. Cardiovasc Drug Rev 24 3-4: 189-203. ^ Crofford, LJ 2008. Pain management in fibromyalgia. Curr Opin Rheumatol 20 3: 246-250. ^ Mathias, Christopher J 2008. L-dihydroxyphenylserine Droxidopa in the treatment of orthostatic hypotension. Clin Auton Res 18 Supplement 1: 25-29. ^ Search of: Droxidopa - List Results - ClinicalTrials.gov External Links Clintrials.gov Chelsea Therapeutics Vanderbilt Autonomic Dysfunction Center v d e Anti-parkinson drugs: dopaminergic agents N04B Dopa and derivatives Droxidopa Levodopa Melevodopa Etilevodopa Adamantane derivatives Amantadine Dopamine agonists A-412,997 Apomorphine Bromocriptine Cabergoline Dihydrexidine Dihydroergocryptine mesylate Fenoldopam Lisuride Pergolide Piribedil Pramipexole Propylnorapomorphine Quinpirole Ropinirole Rotigotine SKF 38393 SKF 82958 MAOIs B Selegiline Rasagiline COMT inhibitors Entacapone Tolcapone Other Budipine dopa decarboxylase inhibitor Carbidopa Retrieved from http://en..org/wiki/Droxidopa Categories: Amino acids | Prodrugs Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Deutsch This page was last modified on 8 August 2008, at 01:43
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