L-threo-dihydroxyphenylserine
L-threo-dihydroxyphenylserine Uses, Dosage, Side Effects, Food Interaction and all others data.
L-threo-dihydroxyphenylserine 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.
L-threo-dihydroxyphenylserine 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.
| Trade Name | L-threo-dihydroxyphenylserine |
| Availability | Prescription only |
| Generic | Droxidopa |
| Droxidopa Other Names | DOPS, Droxidopa, L-Dihydroxyphenylserine, L-DOPS, L-threo-dihydroxyphenylserine |
| Related Drugs | midodrine, phenylephrine, norepinephrine, ephedrine, Levophed, ProAmatine |
| Type | |
| Formula | C9H11NO5 |
| Weight | Average: 213.189 Monoisotopic: 213.063722458 |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
L-threo-dihydroxyphenylserine is a medication used to treat symptomatic neurogenic orthostatic hypotension (nOH) caused by dopamine beta-hydroxylase deficiency, non-diabetic autonomic neuropathy and primary autonomic failure caused by conditions such as Parkinson's disease.
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.
L-threo-dihydroxyphenylserine is also used to associated treatment for these conditions: Symptomatic Neurogenic Orthostatic Hypotension
How L-threo-dihydroxyphenylserine works
L-threo-dihydroxyphenylserine crosses the blood-brain barrier where it is converted to norepinephrine via decarboxylation by L-aromatic-amino-acid decarboxylase. Norephinephrine acts at alpha-adrenergic receptors as a vasoconstrictor and at beta-adrenergic receptors as a heart stimulator and artery dilator.
Toxicity
L-threo-dihydroxyphenylserine 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.
Food Interaction
- Take with or without food. Take consistently with regard to food.
L-threo-dihydroxyphenylserine Hypertension interaction
[Moderate] L-threo-dihydroxyphenylserine is directly metabolized in vivo to norepinephrine via decarboxylation.
As such, it may exacerbate certain cardiovascular conditions by increasing blood pressure and heart rate.
Therapy with droxidopa should be considered cautiously in patients with ischemic heart disease, arrhythmias, or congestive heart failure.
Additionally, droxidopa may exacerbate supine hypertension in patients with neurogenic orthostatic hypotension.
Patients should be advised to elevate the head of the bed while resting or sleeping.
Blood pressure should be monitored both in supine position and the head- elevated sleeping position.
If hypertension persists, then droxidopa dosage should be reduced or discontinued.
If hypertension is not well managed, it can increase the risk of cardiovascular events, especially stroke.
L-threo-dihydroxyphenylserine Drug Interaction
Moderate: amphetamine / dextroamphetamine, sumatriptanUnknown: ibuprofen, onabotulinumtoxinA, loratadine, ivabradine, duloxetine, acetazolamide, omega-3 polyunsaturated fatty acids, fluticasone nasal, fluticasone, fluticasone, pyridostigmine, metoprolol, polyethylene glycol 3350, topiramate, cyanocobalamin, cholecalciferol, ondansetron, sertraline
L-threo-dihydroxyphenylserine Disease Interaction
Moderate: ischemic heart disease/arrhythmias/CHF, renal impairment
Elimination Route
Oral bioavailability is 90%.
Half Life
2-3 hours.
Elimination Route
L-threo-dihydroxyphenylserine is mainly excreted in the urine, with the main metabolite being 3-O-methyldihydroxyphenylserine.
Innovators Monograph
You find simplified version here L-threo-dihydroxyphenylserine
