Alleviating Neurogenic Orthostatic Hypotension

A synthetic amino acid shows promise in the treatment of orthostatic hypotension (OH) in patients with multiple system atrophy (MSA) or Parkinson's disease (PD).

Droxidopa--an orally active synthetic derivative of the natural amino acid L-serine--significantly reduced the fall in orthostatic systolic blood pressure (SBP) in a preliminary European phase IIb trial of its efficacy in the treatment of neurogenic orthostatic hypotension (NOH). The study was conducted at 30 centers in the European Union (EU) and consisted of 125 randomized patients. Patients received either placebo or Droxidopa three times daily for 28 days, in doses ranging from 100–300 mg. The fall in orthostatic SBP was demonstrated at 300 mg with the difference in SBP being 11.6 mm Hg between the groups. The results of the trial also validated the tolerability of Droxidopa, which exhibited no difference in the incidence or severity of adverse events or laboratory values when compared to placebo.

Droxidopa (L-threo-dihydroxyphenylserine), licensed by Chelsea Therapeutics International (Charlotte, NC, USA) from Dainippon Sumitomo Pharma (DSP, Osaka, Japan), is currently approved and marketed in Japan for the treatment of OH. By replenishing depleted norepinephrine via an endogenous enzymatic pathway, Droxidopa allows for re-uptake of norepinephrine into peripheral nervous system neurons, stimulating receptors for vasoconstrinction and providing physiologic improvement in symptomatic NOH patients.

"Of particular interest was our finding that therapeutic benefit was also demonstrated in patients taking dopamine decarboxylase inhibitors,” said lead investigator Dr. Christopher Mathias, Ph.D., D.Sc, FRCP, a professor of neurovascular medicine at Imperial College School of Medicine (London, UK). "Given the typically complex treatment programs for patients suffering from PD and MSA, the demonstrated efficacy of Droxidopa when administered in addition to these widely prescribed medications could have a beneficial impact on the possible therapeutic applications of Droxidopa.”

Symptomatic NOH is a neurogenic disorder resulting from a deficient release of norepinephrine, which results in decreased blood pressure when a person assumes a standing position, and is characterized by lightheadedness, dizziness, blurred vision, and syncope.



Related Links:
Chelsea Therapeutics
Dainippon Sumitomo Pharma