L-Dops and the Treatment of Neurogenic Orthostatic Hypotension

Abstract

L-threo-dihydroxyphenylserine (L-DOPS) is an oral prodrug that is converted to the sympathetic neurotransmitter noradrenaline through a single-step decarboxylation by the endogenous enzyme 3,4-dihydrophenylalanine decarboxylase. DOPS can provide an exogenous source of noradrenaline to adrenergic neurons that are involved in the maintenance of blood pressure. Impaired secretion of noradrenaline at the synaptic junction can result in neurogenic orthostatic hypotension and cause faints and falls. The safety and efficacy of DOPS has been evaluated in patients with neurogenic orthostatic hypotension caused by a variety of neurological conditions that can result in autonomic failure, such as Parkinson’s disease, multiple system atrophy, pure autonomic failure and dopamine-β-hydroxylase deficiency. In this review, we include Phase II and III clinical trials undertaken that have examined the safety, efficacy and tolerability of DOPS in the treatment of neurogenic orthostatic hypotension. Drug mechanisms and pharmacology of the drug are also discussed.