Advanced search
Publication Cover
Future Neurology Volume 8, 2013 - Issue 4
Submit an article Journal homepage
53
Views
0
CrossRef citations to date
0
Altmetric
Drug Evaluation

L-Dops and the Treatment of Neurogenic Orthostatic Hypotension

Ekawat Vichayanrat1 Autonomic & Neurovascular Medicine Unit, Division of Brain Sciences, Medicine, Imperial College London at St Mary‘s Hospital, Praed Street, London, W2 1NY, UK;2 Autonomic Unit, National Hospital for Neurology & Neurosurgery, Queen Square, Division of Clinical Neurology, Institute of Neurology, University College London, London, UKView further author information
,
David A Low1 Autonomic & Neurovascular Medicine Unit, Division of Brain Sciences, Medicine, Imperial College London at St Mary‘s Hospital, Praed Street, London, W2 1NY, UK;2 Autonomic Unit, National Hospital for Neurology & Neurosurgery, Queen Square, Division of Clinical Neurology, Institute of Neurology, University College London, London, UKView further author information
,
Masato Asahina3 Department of Neurology, Chiba University School of Medicine, Chiba, JapanView further author information
,
Andrew P Owens1 Autonomic & Neurovascular Medicine Unit, Division of Brain Sciences, Medicine, Imperial College London at St Mary‘s Hospital, Praed Street, London, W2 1NY, UK;2 Autonomic Unit, National Hospital for Neurology & Neurosurgery, Queen Square, Division of Clinical Neurology, Institute of Neurology, University College London, London, UKView further author information
,
Valeria Iodice1 Autonomic & Neurovascular Medicine Unit, Division of Brain Sciences, Medicine, Imperial College London at St Mary‘s Hospital, Praed Street, London, W2 1NY, UK;2 Autonomic Unit, National Hospital for Neurology & Neurosurgery, Queen Square, Division of Clinical Neurology, Institute of Neurology, University College London, London, UKView further author information
,
Gianluigi Galizia4 Division of Physical Medicine & Rehabilitation, Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Veruno, Veruno(NO), ItalyView further author information
&
Christopher J Mathias1 Autonomic & Neurovascular Medicine Unit, Division of Brain Sciences, Medicine, Imperial College London at St Mary‘s Hospital, Praed Street, London, W2 1NY, UK;2 Autonomic Unit, National Hospital for Neurology & Neurosurgery, Queen Square, Division of Clinical Neurology, Institute of Neurology, University College London, London, UKCorrespondence[email protected]
View further author information
 show all
Pages 381-397 | Published online: 05 Jul 2013

References

  • Lahrmann H , CortelliP, HilzM, MathiasCJ, StruhalW, TassinariM. EFNS guidelines on the diagnosis and management of orthostatic hypotension. Eur. J. Neurol.13(9), 930–936 (2006).
  • Freeman R , WielingW, AxelrodFBet al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin. Auton. Res.21(2), 69–72 (2011).
  • Jamnadas-Khoda J , KoshyS, MathiasCJ, MuthaneUB, RagothamanM, DodaballapurSK. Are current recommendations to diagnose orthostatic hypotension in Parkinson‘s disease satisfactory? Mov. Disord.24(12), 1747–1751 (2009).
  • Gilman S , WenningGK, LowPAet al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology71(9), 670–676 (2008).
  • Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. The Consensus Committee of the American Autonomic Society and the American Academy of Neurology. Neurology46(5), 1470 (1996).
  • Wenning GK , ColosimoC, GeserF, PoeweW. Multiple system atrophy. Lancet Neurol.3(2), 93–103 (2004).
  • Bower JH , MaraganoreDM, McDonnellSK, RoccaWA. Incidence of progressive supranuclear palsy and multiple system atrophy in Olmsted County, Minnesota, 1976 to 1990. Neurology49(5), 1284–1288 (1997).
  • Luukinen H , KoskiK, LaippalaP, KivelaSL. Prognosis of diastolic and systolic orthostatic hypotension in older persons. Arch. Intern. Med.159(3), 273–280 (1999).
  • Mathias C . Disorders of the autonomic nervous system. In: Oxford Textbook of Medicine. WarrellDA, CoxTM, FirthJD(Eds) . Oxford University Press, Oxford, UK, 5055–5068 (2010).
  • Hobson P , GallacherJ, MearaJ. Cross-sectional survey of Parkinson‘s disease and parkinsonism in a rural area of the United Kingdom. Mov. Disord.20(8), 995–998 (2005).
  • Mutch WJ , Dingwall-FordyceI, DownieAW, PatersonJG, RoySK. Parkinson‘s disease in a Scottish city. Br. Med. J. Clin. Res.292(6519), 534–536 (1986).
  • Velseboer DC , De Haan RJ, Wieling W, Goldstein DS, De Bie RM. Prevalence of orthostatic hypotension in Parkinson‘s disease: a systematic review and meta-analysis. Parkinsonism Relat. Disord.17(10), 724–729 (2011).
  • Timmers HJ , DeinumJ, WeversRA, LendersJW. Congenital dopamine-β-hydroxylase deficiency in humans. Ann. NY Acad. Sci.1018, 520–523 (2004).
  • Edwards JL , VincentAM, ChengHT, FeldmanEL. Diabetic neuropathy: mechanisms to management. Pharmacol. Ther.120(1), 1–34 (2008).
  • Dardiotis E , KoutsouP, PapanicolaouEZet al. Epidemiological, clinical and genetic study of familial amyloidotic polyneuropathy in Cyprus. Amyloid16(1), 32–37 (2009).
  • Mathias CJ , MallipeddiR, Bleasdale-BarrK. Symptoms associated with orthostatic hypotension in pure autonomic failure and multiple system atrophy. J. Neurol.246(10), 893–898 (1999).
  • Goldstein DS , SharabiY. Neurogenic orthostatic hypotension: a pathophysiological approach. Circulation119(1), 139–146 (2009).
  • Vellas BJ , WayneSJ, RomeroLJ, BaumgartnerRN, GarryPJ. Fear of falling and restriction of mobility in elderly fallers. Age Ageing26(3), 189–193 (1997).
  • Masaki KH , SchatzIJ, BurchfielCMet al. Orthostatic hypotension predicts mortality in elderly men: the Honolulu Heart Program. Circulation98(21), 2290–2295 (1998).
  • Eigenbrodt ML , RoseKM, CouperDJ, ArnettDK, SmithR, JonesD. Orthostatic hypotension as a risk factor for stroke: the atherosclerosis risk in communities (ARIC) study, 1987–1996. Stroke J. Cereb. Circ.31(10), 2307–2313 (2000).
  • Rose KM , TyrolerHA, NardoCJet al. Orthostatic hypotension and the incidence of coronary heart disease: the Atherosclerosis Risk in Communities study. Am. J. Hypertens.13(6 Pt 1), 571–578 (2000).
  • Fedorowski A , EngstromG, HedbladB, MelanderO. Orthostatic hypotension predicts incidence of heart failure: the Malmo preventive project. Am. J. Hypertens.23(11), 1209–1215 (2010).
  • Goldstein DS , HolmesC, SharabiY, BrentzelS, EisenhoferG. Plasma levels of catechols and metanephrines in neurogenic orthostatic hypotension. Neurology60(8), 1327–1332 (2003).
  • Hussain RM , McIntoshSJ, LawsonJ, KennyRA. Fludrocortisone in the treatment of hypotensive disorders in the elderly. Heart Br. Cardiac Soc.76(6), 507–509 (1996).
  • Low PA , GildenJL, FreemanR, ShengKN, McElligottMA. Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. A randomized, double-blind multicenter study. Midodrine Study Group. JAMA277(13), 1046–1051 (1997).
  • Wright RA , KaufmannHC, PereraRet al. A double-blind, dose-response study of midodrine in neurogenic orthostatic hypotension. Neurology51(1), 120–124 (1998).
  • Robertson D , DavisTL. Recent advances in the treatment of orthostatic hypotension. Neurology45(4 Suppl. 5), S26–S32 (1995).
  • Rosenmund KW , DornsaftH. [Oxy-and dioxyphenyl-serine and the parent substance of adrenaline]. Ber. Dtsch Chem.52(8), 1734–1749 (1919).
  • Blaschko H , HoltonP, StanleyGH. The decarboxylation of -3: 4-dihydroxyphenylserine (noradrenaline carboxylic acid). Br. J. Pharmacol. Chemother.3(4), 315–319 (1948).
  • Blaschko H , BurnJH, LangemannH. The formation of noradrenaline from dihydroxyphenylserine. Br. J. Pharmacol. Chemother.5(3), 431–437 (1950).
  • Beyer KH , BlaschkoH, BurnJH, LangemannH. Enzymic formation of noradrenaline in mammalian tissue extracts. Nature165(4206), 926 (1950).
  • Araki H , TanakaC, FujiwaraH, NakamuraM, OhmuraI. Pressor effect of L-threo-3,4-dihydroxyphenylserine in rats. J. Pharm. Pharmacol.33(12), 772–777 (1981).
  • Birkmayer W , BirkmayerG, LechnerH, RiedererP. DL-3,4-threo-DOPS in Parkinson‘s disease: effects on orthostatic hypotension and dizziness. J. Neural Transm.58(3–4), 305–313 (1983).
  • Sakoda S , SuzukiT, HigaSet al. Treatment of orthostatic hypotension in Shy-Drager syndrome with DL-threo-3,4-dihydroxyphenylserine: a case report. Eur. Neurol.24(5), 330–334 (1985).
  • Suzuki T , HigaS, SakodaSet al. Orthostatic hypotension in familial amyloid polyneuropathy: treatment with DL-threo-3,4-dihydroxyphenylserine. Neurology31(10), 1323–1326 (1981).
  • Suzuki T , HigaS, TsugeIet al. Effect of infused L-threo-3,4-dihydroxyphenylserine on adrenergic activity in patients with familial amyloid polyneuropathy. Eur. J. Clin. Pharmacol.17(6), 429–435 (1980).
  • Biaggioni I , RobertsonD. Endogenous restoration of noradrenaline by precursor therapy in dopamine-β-hydroxylase deficiency. Lancet2(8569), 1170–1172 (1987).
  • Mathias CJ , BannisterRB, CortelliPet al. Clinical, autonomic and therapeutic observations in two siblings with postural hypotension and sympathetic failure due to an inability to synthesize noradrenaline from dopamine because of a deficiency of dopamine β hydroxylase. Q. J. Med.75(278), 617–633 (1990).
  • Narabayashi H , KondoT, YokochiF, NagatsuT. Clinical effects of L-threo-3,4-dihydroxyphenylserine in cases of parkinsonism and pure akinesia. Adv. Neurol.45, 593–602 (1987).
  • Ossipov MH , DussorGO, PorrecaF. Central modulation of pain. J. Clin. Invest.120(11), 3779–3787 (2010).
  • Benarroch EE . The locus ceruleus norepinephrine system: functional organization and potential clinical significance. Neurology73(20), 1699–1704 (2009).
  • Takagi H , HarimaA. Analgesic effect of L-threo-3,4-dihydroxyphenylserine (L-DOPS) in patients with chronic pain. Eur. Neuropsychopharmacol.6(1), 43–47 (1996).
  • Otsuka M , ShimizuN, DohbutsuMet al. L-threo-3,4-dihydroxyphenylserine treatment for dementia of various etiology. Neurol. Ther.5(4), 355–360 (1988).
  • Kalinin S , PolakPE, LinSX, SakharkarAJ, PandeySC, FeinsteinDL. The noradrenaline precursor L-DOPS reduces pathology in a mouse model of Alzheimer‘s disease. Neurobiol. Aging33(8), 1651–1663 (2012).
  • Hirayama E , YamagamiA, OnishiH, MuiK, FukushimaK, KawakitaY. Clinical trial of L-threo-DOPS on depression and depressive state. Jpn Pharmacol. Ther.220(3), 957–964 (1992).
  • Kachi T , IwaseS, ManoT, SaitoM, KunimotoM, SobueI. Effect of L-threo-3,4-dihydroxyphenylserine on muscle sympathetic nerve activities in Shy-Drager syndrome. Neurology38(7), 1091–1094 (1988).
  • Inagaki C , FujiwaraH, TanakaC. Inhibitory effect of (+)threo-3,4-dihydroxy-phenylserine (DOPS) on decarboxylation of (-)threo-dops. Jpn J. Pharmacol.26(3), 380–382 (1976).
  • Hoeldtke RD , CilmiKM, Mattis-GravesK. DL-Threo-3,4-dihydroxyphenylserine does not exert a pressor effect in orthostatic hypotension. Clin. Pharmacol. Ther.36(3), 302–306 (1984).
  • Suzuki T , HigaS, SakodaSet al. Pharmacokinetic studies of oral L-threo-3,4-dihydroxyphenylserine in normal subjects and patients with familial amyloid polyneuropathy. Eur. J. Clin. Pharmacol.23(5), 463–468 (1982).
  • Maruyama W , NaoiM, NarabayashiH. [Study on the metabolism of droxidopa in humans]. Rinsho Shinkeigaku34(10), 991–995 (1994).
  • Maruyama W , NaoiM, NarabayashiH. The metabolism of L-DOPA and L-threo-3,4-dihydroxyphenylserine and their effects on monoamines in the human brain: analysis of the intraventricular fluid from parkinsonian patients. J. Neurol. Sci.139(1), 141–148 (1996).
  • Naoi M , TakahashiT, KunoN, NagatsuT. L-threo-3,4-dihydroxyphenylserine (DOPS) aldolase: a new enzyme cleaving DOPS into protocatechualdehyde and glycine. Biochem. Biophys. Res. Commun.143(2), 482–488 (1987).
  • Ichinose H , Sumi-IchinoseC, OhyeT, HaginoY, FujitaK, NagatsuT. Tissue-specific alternative splicing of the first exon generates two types of mRNAs in human aromatic L-amino acid decarboxylase. Biochemistry31(46), 11546–11550 (1992).
  • Goldstein DS , HolmesC, KaufmannH, FreemanR. Clinical pharmacokinetics of the norepinephrine precursor L-threo-DOPS in primary chronic autonomic failure. Clin. Auton. Res.14(6), 363–368 (2004).
  • Goldstein DS , HolmesC, SewellL, PechnikS, KopinIJ. Effects of carbidopa and entacapone on the metabolic fate of the norepinephrine prodrug L-DOPS. J. Clin. Pharmacol.51(1), 66–74 (2011).
  • Matsubara S , SawaY, YokojiH, TakamoriM. Shy-Drager syndrome. Effect of fludrocortisone and L-threo-3,4-dihydroxyphenylserine on the blood pressure and regional cerebral blood flow. J. Neurol. Neurosurg. Psychiatry53(11), 994–997 (1990).
  • Yoshizawa T , FujitaT, MizusawaH, ShojiS. L-threo-3,4-dihydroxyphenylserine enhances the orthostatic responses of plasma renin activity and angiotensin II in multiple system atrophy. J. Neurol.246(3), 193–197 (1999).
  • Kaufmann H , SaadiaD, VoustianioukAet al. Norepinephrine precursor therapy in neurogenic orthostatic hypotension. Circulation108(6), 724–728 (2003).
  • Iida N , TsubakiharaY, ShiraiD, ImadaA, SuzukiM. Treatment of dialysis-induced hypotension with L-threo-3,4-dihydroxyphenylserine. Nephrol. Dial. Transplant.9(8), 1130–1135 (1994).
  • Freeman R , LandsbergL, YoungJ .The treatment of neurogenic orthostatic hypotension with 3,4-DL-threo-dihydroxyphenylserine: a randomized, placebo-controlled, crossover trial. Neurology53(9), 2151–2157 (1999).
  • Freeman R , YoungJ, LandsbergL, LipsitzL. The treatment of postprandial hypotension in autonomic failure with 3,4-DL-threo-dihydroxyphenylserine. Neurology47(6), 1414–1420 (1996).
  • Carvalho MJ , Van Den MeirackerAH, BoomsmaFet al. Improved orthostatic tolerance in familial amyloidotic polyneuropathy with unnatural noradrenaline precursor L-threo-3,4-dihydroxyphenylserine. J. Auton. Nerv. Syst.62(1–2), 63–71 (1997).
  • Ando Y , GotohT, KawaguchiY, TanakaY, SakashitaN, AndoM. Intranasal L-threo-3,4,-dihydroxyphenylserine in treating diarrhea associated with familial amyloidotic polyneuropathy. Pharmacotherapy15(3), 345–349 (1995).
  • Wecht J , Rosado-RiveraD, YenC, RadulovicM, BaumanW. Blood pressure effect of droxidopa in hypotensive individuals with spinal cord injury. Clin. Auton. Res.22, 254 (2012).
  • Kaufmann H , OribeE, YahrMD. 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(2), 143–148 (1991).
  • Mathias CJ , SenardJM, BrauneSet al. 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(4), 235–242 (2001).
  • Mathias CJ . L-dihydroxyphenylserine (Droxidopa) in the treatment of orthostatic hypotension: the European experience. Clin. Auton. Res.18(Suppl. 1), S25–S29 (2008).
  • Mathias CJ , SenardJM, CortelliP. A double-blind, randomized, placebo-controlled study to determine the efficacy and safety of droxidopa in the treatment of orthostatic hypotension associated with multiple system atrophy or Parkinson‘s disease. Clin. Auton. Res.17, 272 (2007).
  • Yanagisawa N , IkedaS, HashimotoTet al. [Effects of L-threo-Dops on orthostatic hypotension in Parkinson‘s disease]. No To Shinkei50(2), 157–163 (1998).
  • Kaufmann H , MalamutR, Norcliffe-KaufmannL, RosaK, FreemanR. The Orthostatic Hypotension Questionnaire (OHQ): validation of a novel symptom assessment scale. Clin. Auton. Res.22(2), 79–90 (2012).
  • Mathias CJ , LowP, FreemanR, HewittA, KaufmannH. Integrated efficacy analysis of droxidopa in 2 double-blind, placebo-controlled Phase 3 studies in patients with neurogenic orthostatic hypotension. Mov. Disord.27(Suppl. 1), S1296 (2012).
  • Kaufmann H , FreemanR, BiaggioniIet al. Treatment of neurogenic orthostatic hypotension with droxidopa: results from a multi-center, double-blind, randomized, placebo-controlled, parallel group, induction design study (PL02.001). Neurology78(Meeting Abstracts 1), PL02.001 (2012).
  • Wenning G , LowP, SzakacsC, KaufmannH. Orthostatic hypotension questionnaire composite score in patients with neurogenic orthostatic hypotension treated with droxidopa. Mov. Disord.27(Suppl. 1), 1305 (2012).
  • Biaggioni I , LowP, RowseG, KaufmannH. Analysis of efficacy in patients with symptomatic neurogenic orthostatic hypotension treated with droxidopa and dopa-decarboxylase inhibitors. Mov. Disord.27(Suppl. 1), 1284 (2012).
  • Wenning GK , KaufmannH, MathiasCJ, CortelliP. Safety and efficacy of Northera (droxidopa) in multiple system atrophy. Mov. Disord.26(Suppl. 2), 778 (2011).
  • Low P , NelsonJ, StacyM. Safety and efficacy of droxidopa in patients previously treated with midodrine. Mov. Disord.27(Suppl. 1), 1295 (2012).
  • Isaacson S , ShillH, VerninoS, CioffiC, HutchmanR. Durability of effect with long-term, open-label droxidopa treatment in patients with symptomatic neurogenic orthostatic hypotension (NOH 303). Mov. Disord.27(Suppl. 1), 1291 (2012).
  • Hauser RA , SchweitermanW, IsaacsonS. Impact of treatment with droxidopa in repeat fallers with parkinson‘s disease and symptomatic neurogenic orthostatic hypotension. Mov. Disord.27(Suppl. 1), 1287 (2012).
  • Shill H , VerninoS, HutchmanR, AdkinsL, IsaacsonS. A multicenter, open-label study to assess the long-term safety of droxidopa in patients with symptomatic neurogenic orthostatic hypotension. Mov. Disord.27(Suppl. 1), 1302 (2012).
  • Mathias CJ , BannisterR. Dopamine β-hydroxylase deficiency – with a note on other genetically determined causes of autonomic failure. In: Autonomic Failure: A Textbook of Clinical Disorders of the Autonomic Nervous System (5th Edition). MathiasCJ, BannisterR(Eds) . Oxford University Press, Oxford, UK, 597–612 (2013).
  • Goldstein DS . L-Dihydroxyphenylserine (L-DOPS): a norepinephrine prodrug. Cardiovasc. Drug Rev.24(3–4), 189–203 (2006).
  • Kaufmann H , MathiasCJ, FreemanR, LowP, Biaggioni I; the Droxidopa Study Group. Treatment with droxidopa – a Phase III multinational, placebo-controlled, parallel group, withdrawal-design study in subjects with neurogenic orthostatic hypotension and non-diabetic autonomic neuropathy. Clin.Auton. Res.19(5), Abstract 281 (2009).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.