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L-threo-3,4-dihydroxyphenylserine (droxidopa), a pro-drug metabolized to norepinephrine in nerve endings and other tissues, has been commercially available in Japan since 1989 for treating orthostatic hypotension symptoms in Parkinson's disease (PD) patients with a Hoehn & Yahr stage III rating, as well as patients with Multiple System Atrophy (MSA), familial amyloid polyneuropathy, and hemodialysis. Recently, the FDA has approved its use in symptomatic neurogenic orthostatic hypotension (NOH). Areas covered: The authors review the effects of droxidopa in NOH with a focus on the neurodegenerative diseases PD, MSA, and pure autonomic failure (PAF). Expert opinion: A few small and short placebo-controlled clinical trials in NOH showed significant reductions in the manometric drop in blood pressure (BP) after posture changes or meals. Larger Phase III studies showed conflicting results, with two out of four trials meeting their primary outcome and thus suggesting a positive yet short-lasting effect of the drug on OH Questionnaire composite score, light-headedness/dizziness score, and standing BP during the first two treatment-weeks. Results appear essentially similar in PD, MSA, and PAF. The FDA granted droxidopa approval in the frame of an 'accelerated approval program' provided further studies are conducted to assess its long-term effects on OH symptoms.
This article was published in the following journal.
Name: Expert opinion on pharmacotherapy
Arterial hypotension is a frequently encountered phenomenon in clinical practice. It is responsible for multiple consultations and/or hospitalizations, mostly in elderly people. It is associated with ...
Orthostatic hypotension (OH) is the key manifestation of autonomic dysfunction with many causes. Systemic neurological causes such as paraneoplastic syndrome are usually ignored.
Orthostatic hypotension (OH) is common in older adults with reported prevalence rates of 5-40%. A direct link between OH and cognitive performance has been proposed due to impaired vascular autoregula...
The purpose of this study is to see whether droxidopa is effective in treating symptoms of neurogenic orthostatic hypotension in patients with Primary Autonomic Failure (Pure Autonomic Fai...
The purpose of this study is to see whether the durability of effect of Droxidopa in treating symptoms of neurogenic orthostatic hypotension in patients with Primary Autonomic Failure (Pur...
To evaluate the time to treatment intervention in patients with Parkinson's Disease (PD), Multiple System Atrophy (MSA), Pure Autonomic Failure (PAF), Non-Diabetic Autonomic Neuropathy (ND...
This multiple-center, randomized, 2 part, single- and double-blind study will be conducted in male and female subjects with neurogenic orthostatic hypotension to evaluate the effect of TD-...
Symptomatic NOH in patients with primary autonomic failure is thought to be a consequence of norepinephrine depletion leading to a diminished capacity to effect an appropriate cardiovascul...
Symptoms of cerebral hypoperfusion or autonomic overaction which develop while the subject is standing, but are relieved on recumbency. Types of this include NEUROCARDIOGENIC SYNCOPE; POSTURAL ORTHOSTATIC TACHYCARDIA SYNDROME; and neurogenic ORTHOSTATIC HYPOTENSION. (From Noseworthy, JH., Neurological Therapeutics Principles and Practice, 2007, p2575-2576)
A precursor of noradrenaline that is used in the treatment of parkinsonism. The racemic 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. Administration of DL-threo-3,4-dihydroxyphenylserine has been claimed to result in an improvement in this phenomenon but controlled studies have failed to demonstrate improvement. (Reynolds JEF(Ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc, Englewood, CO, 1995)
A significant drop in BLOOD PRESSURE after assuming a standing position. Orthostatic hypotension is a finding, and defined as a 20-mm Hg decrease in systolic pressure or a 10-mm Hg decrease in diastolic pressure 3 minutes after the person has risen from supine to standing. Symptoms generally include DIZZINESS, blurred vision, and SYNCOPE.
A syndrome of ORTHOSTATIC INTOLERANCE combined with excessive upright TACHYCARDIA, and usually without associated ORTHOSTATIC HYPOTENSION. All variants have in common an excessively reduced venous return to the heart (central HYPOVOLEMIA) while upright.
An autosomal disorder of the peripheral and autonomic nervous systems limited to individuals of Ashkenazic Jewish descent. Clinical manifestations are present at birth and include diminished lacrimation, defective thermoregulation, orthostatic hypotension (HYPOTENSION, ORTHOSTATIC), fixed pupils, excessive SWEATING, loss of pain and temperature sensation, and absent reflexes. Pathologic features include reduced numbers of small diameter peripheral nerve fibers and autonomic ganglion neurons. (From Adams et al., Principles of Neurology, 6th ed, p1348; Nat Genet 1993;4(2):160-4)
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