DROXIDOPA

Absorption

Oral bioavailability is 90%.

Toxicity

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.

Description

Droxidopa is a synthetic amino acid precursor of (-)-norepinephrine which is absorbed from the gut and metabolized to norepinephrine. In Parkinsonian patients, droxidopa added to existing levodopa/decarboxylase inhibitor therapy produces significant improvements in retropulsion, dysarthria and muscular rigidity refractory to other treatments; however, tremor was unaffected.

Description

Droxidopa (L-DOPS) is a synthetic precursor and prodrug of the neurotransmitter norepinephrine. It is transformed into norepinephrine through the action of DOPA decarboxylase. L-DOPS increases norepinephrine levels in the rat heart following intraperitoneal administration and in the brain following intracerebroventricular administration at doses of 125 and 100 μg/animal, respectively. It increases arterial pressure and mesenteric arterial resistance in rats with ligated portal vein or biliary ducts when used at doses of 25-50 mg/kg. L-DOPS crosses the blood brain barrier, however, its effects can be blocked by the peripherally-restricted DOPA decarboxylase inhibitor carbidopa , indicating that the mechanism is peripheral. Formulations containing droxidopa are used in the treatment of neurogenic orthostatic hypotension.

Chemical properties

Off-White Solid

Originator

Sumitomo (Japan)

The Uses of DROXIDOPA

The L-threo-form Droxidopa. A synthetic amino acid precursor of Norepinephrine (N674500). Antiparkinsonian.

The Uses of DROXIDOPA

Droxidopa is a psychoactive drug and acts as a prodrug to the neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline).

The Uses of DROXIDOPA

L-DOPS has been administered for clinical trial studies in mice with amyloid pathology.

Background

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.

Indications

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.

Definition

ChEBI: A serine derivative that is L-serine substituted at the beta-position by a 3,4-dihydroxyphenyl group. A prodrug for noradrenalone, it is used for treatment of neurogenic orthostatic hypotension

brand name

DOPS

General Description

L-DOPS, also called L-threo 3,4-Dihydroxyphenylserine or droxidopa is a catecholamine. L-DOPS has many clinical advantages and may be useful for treating norepinephrine deficiency. It is used for treating neurogenic orthostatic hypotension and improves norepinephrine levels. L-DOPS mediates reduction of amyloid plaques and could have a therapeutic potential for treating amyloid pathology.

Biochem/physiol Actions

L-DOPS is a norepinephrine precursor in vivo.

Pharmacokinetics

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.

Metabolism

Droxidopa is metabolized by aromatic L-amino acid decarboxylase.