Abstract
Neurogenic orthostatic hypotension results from failure to release norepinephrine, the neurotransmitter of sympathetic postganglionic neurons, appropriately upon standing. In double blind, cross over, placebo controlled trials, administration of droxidopa, a synthetic amino acid that is decarboxylated to norepinephrine by the enzyme l-aromatic amino acid decarboxylase increases standing blood pressure, ameliorates symptoms of orthostatic hypotension and improves standing ability in patients with neurogenic orthostatic hypotension due to degenerative autonomic disorders. The pressor effect results from conversion of droxidopa to norepinephrine outside the central nervous system both in neural and non-neural tissue. This mechanism of action makes droxidopa effective in patients with central and peripheral autonomic disorders.
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References
Bartholini J, Constantinidis J, Puig M, Tissot R, Pletscher A (1975) The stereoisomers of 3,4-dihydroxyphenylserine as precursors of norepinephrine. J Pharmacol Exp Ther 193:523–532
Biaggioni I, Robertson D (1987) Endogenous restoration of noradrenaline by precursor therapy in dopamine-beta-hydroxylase deficiency. Lancet 2:1170–1172
Blaschko H, Burn JH, Langemann H (1950) The formation of noradrenaline from dihydroxyphenylserine. Br J Pharmacol 5:431–437
Freeman R, Landsberg L, Young J (1999) The treatment of neurogenic orthostatic hypotension with 3,4-dl-threo-dihydroxyphenylserine: a randomized, placebo-controlled, crossover trial. Neurology 53:2151–2157
Gibbons CH, Vernino SA, Kaufmann H, Freeman R (2005) l-DOPS therapy for refractory orthostatic hypotension in autoimmune autonomic neuropathy. Neurology 65:1104–1106
Goldstein DS, Holmes C, Kaufmann H, Freeman R (2004) Clinical pharmacokinetics of the norepinephrine precursor l-threo-DOPS in primary chronic autonomic failure. Clin Auton Res 14:363–368
Hague K, Lento P, Morgello S, Caro S, Kaufmann H (1997) The distribution of Lewy bodies in pure autonomic failure: autopsy findings and review of the literature. Acta Neuropathol (Berl) 94:192–196
Inagaki C, Fujiwara H, Tanaka C (1976) Inhibitory effect of (+)threo-3,4-dihydroxy-phenylserine (DOPS) on decarboxylation of (−)threo-dops. Jpn J Pharmacol 26:380–382 Issn: 0021-5198
Kaufmann H (1996) Could treatment with DOPS do for autonomic failure what DOPA did for Parkinson’s disease? Neurology 47:1370–1371
Kaufmann H, Oribe E, Yahr MD (1991) Differential effect of l-threo-3,4-dihydroxyphenylserine in pure autonomic failure and multiple system atrophy with autonomic failure. J Neural Transm Park Dis Dement Sect 3:143–148
Kaufmann H, Saadia D, Voustianiouk A, Goldstein DS, Holmes C, Yahr MD, Nardin R, Freeman R (2003) Norepinephrine precursor therapy in neurogenic orthostatic hypotension. Circulation 108:724–728
Man in’t Veld AJ, Boomsma F, van den Meiracker AH, Schalekamp MA (1987) Effect of unnatural noradrenaline precurser on sympathetic control and orthostatic hypotension in dopamine-beta-hydroxylase defficiency. Lancet 2:1172–1175
Mathias CJ, Senard JM, Braune S, Watson L, Aragishi A, Keeling JE, Taylor MD (2001) l-threo-dihydroxyphenylserine (l-threo-DOPS; droxidopa) in the management of neurogenic orthostatic hypotension: a multi-national, multi-center, dose-ranging study in multiple system atrophy and pure autonomic failure. Clin Auton Res 11:235–242
Polinsky RJ, Kopin IJ, Ebert MH, Weise V (1981) Pharmacologic distinction of different orthostatic hypotension syndromes. Neurology 31:1–7
Schmiterlow CG (1951) The formation in vivo of noradrenaline from 3:4-dihydroxyphenylserine (noradrenaline carboxylic acid). Br J Pharmacol 6:127–134
Suzuki T, Higa S, Tsuge I, Sakoda S, Hayashi A, Yamamura Y, Takaba Y, Nakajima A (1980) Effect of infused l-threo-3,4-dihydroxyphenylserine on adrenergic activity in patients with familial amyloid polyneuropathy. Eur J Clin Pharmacol 17:429–435
Acknowledgment
I am grateful to Dr. Lucy Norcliffe-Kaufmann for her help designing the figures. Disclosure Dr. Kaufmann has served as a consultant for Chelsea Therapeutics.
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Kaufmann, H. L-dihydroxyphenylserine (Droxidopa): a new therapy for neurogenic orthostatic hypotension. Clin Auton Res 18 (Suppl 1), 19–24 (2008). https://doi.org/10.1007/s10286-007-1002-2
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DOI: https://doi.org/10.1007/s10286-007-1002-2