Skip to main content
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 2003 Sep;74(9):1294–1298. doi: 10.1136/jnnp.74.9.1294

Acetylcholinesterase inhibition: a novel approach in the treatment of neurogenic orthostatic hypotension

W Singer 1, T Opfer-Gehrking 1, B McPhee 1, M Hilz 1, A Bharucha 1, P Low 1
PMCID: PMC1738643  PMID: 12933939

Abstract

Background: Pharmacological treatment of orthostatic hypotension is often limited because of troublesome supine hypertension.

Objective: To investigate a novel approach to treatment using acetylcholinesterase inhibition, based on the theory that enhanced sympathetic ganglion transmission increases systemic resistance in proportion to orthostatic needs.

Design: Prospective open label single dose trial.

Material: 15 patients with neurogenic orthostatic hypotension caused by: multiple system atrophy (n = 7), Parkinson's disease (n = 3), diabetic neuropathy (n = 1), amyloid neuropathy (n = 1), and idiopathic autonomic neuropathy (n = 3).

Methods: Heart rate, blood pressure, peripheral resistance index (PRI), cardiac index, stroke index, and end diastolic index were monitored continuously during supine rest and head up tilt before and one hour after an oral dose of 60 mg pyridostigmine.

Results: There was only a modest non-significant increase in supine blood pressure and PRI. In contrast, acetylcholinesterase inhibition significantly increased orthostatic blood pressure and PRI and reduced the fall in blood pressure during head up tilt. Orthostatic heart rate was reduced after the treatment. The improvement in orthostatic blood pressure was associated with a significant improvement in orthostatic symptoms.

Conclusions: Acetylcholinesterase inhibition appears effective in the treatment of neurogenic orthostatic hypotension. Orthostatic symptoms and orthostatic blood pressure are improved, with only modest effects in the supine position. This novel approach may form an alternative or supplemental tool in the treatment of orthostatic hypotension, specially for patients with a high supine blood pressure.

Full Text

The Full Text of this article is available as a PDF (140.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brimijoin S., Hammond P., Khraibi A. A., Tyce G. M. Catecholamine release and excretion in rats with immunologically induced preganglionic sympathectomy. J Neurochem. 1994 Jun;62(6):2195–2204. doi: 10.1046/j.1471-4159.1994.62062195.x. [DOI] [PubMed] [Google Scholar]
  2. Camilleri M., Malagelada J. R., Stanghellini V., Fealey R. D., Sheps S. G. Gastrointestinal motility disturbances in patients with orthostatic hypotension. Gastroenterology. 1985 Jun;88(6):1852–1859. doi: 10.1016/0016-5085(85)90010-1. [DOI] [PubMed] [Google Scholar]
  3. Chobanian A. V., Volicer L., Tifft C. P., Gavras H., Liang C. S., Faxon D. Mineralocorticoid-induced hypertension in patients with orthostatic hypotension. N Engl J Med. 1979 Jul 12;301(2):68–73. doi: 10.1056/NEJM197907123010202. [DOI] [PubMed] [Google Scholar]
  4. Cook J. E., Kolka M. A., Wenger C. B. Chronic pyridostigmine bromide administration: side effects among soldiers working in a desert environment. Mil Med. 1992 May;157(5):250–254. [PubMed] [Google Scholar]
  5. Dampney R. A. Functional organization of central pathways regulating the cardiovascular system. Physiol Rev. 1994 Apr;74(2):323–364. doi: 10.1152/physrev.1994.74.2.323. [DOI] [PubMed] [Google Scholar]
  6. Finley J. C., Pascuzzi R. M. Rational therapy of myasthenia gravis. Semin Neurol. 1990 Mar;10(1):70–82. doi: 10.1055/s-2008-1041256. [DOI] [PubMed] [Google Scholar]
  7. Fritsch J. M., Eckberg D. L., Graves L. D., Wallin B. G. Arterial pressure ramps provoke linear increases of heart period in humans. Am J Physiol. 1986 Dec;251(6 Pt 2):R1086–R1090. doi: 10.1152/ajpregu.1986.251.6.R1086. [DOI] [PubMed] [Google Scholar]
  8. Gemmill J. D., Venables G. S., Ewing D. J. Noradrenaline response to edrophonium in primary autonomic failure: distinction between central and peripheral damage. Lancet. 1988 May 7;1(8593):1018–1021. doi: 10.1016/s0140-6736(88)91842-9. [DOI] [PubMed] [Google Scholar]
  9. Kolka M. A., Stephenson L. A. Human temperature regulation during exercise after oral pyridostigmine administration. Aviat Space Environ Med. 1990 Mar;61(3):220–224. [PubMed] [Google Scholar]
  10. Low P. A. Autonomic nervous system function. J Clin Neurophysiol. 1993 Jan;10(1):14–27. doi: 10.1097/00004691-199301000-00003. [DOI] [PubMed] [Google Scholar]
  11. Low P. A. Composite autonomic scoring scale for laboratory quantification of generalized autonomic failure. Mayo Clin Proc. 1993 Aug;68(8):748–752. doi: 10.1016/s0025-6196(12)60631-4. [DOI] [PubMed] [Google Scholar]
  12. Low P. A., Gilden J. L., Freeman R., Sheng K. N., McElligott M. A. Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. A randomized, double-blind multicenter study. Midodrine Study Group. JAMA. 1997 Apr 2;277(13):1046–1051. [PubMed] [Google Scholar]
  13. Low P. A., Opfer-Gehrking T. L., McPhee B. R., Fealey R. D., Benarroch E. E., Willner C. L., Suarez G. A., Proper C. J., Felten J. A., Huck C. A. Prospective evaluation of clinical characteristics of orthostatic hypotension. Mayo Clin Proc. 1995 Jul;70(7):617–622. doi: 10.4065/70.7.617. [DOI] [PubMed] [Google Scholar]
  14. McKinzie S., Tyce G. M., Brimijoin S. Lowered norepinephrine turnover as a sign of impaired ganglionic transmission after preganglionic lesioning by acetylcholinesterase antibodies. J Pharmacol Exp Ther. 1996 May;277(2):817–822. [PubMed] [Google Scholar]
  15. Newman D. G., Callister R. The non-invasive assessment of stroke volume and cardiac output by impedance cardiography: a review. Aviat Space Environ Med. 1999 Aug;70(8):780–789. [PubMed] [Google Scholar]
  16. Nóbrega A. C., Carvalho A. C., Santos K. B., Soares P. P. Cholinergic stimulation with pyridostigmine blunts the cardiac responses to mental stress. Clin Auton Res. 1999 Feb;9(1):11–16. doi: 10.1007/BF02280691. [DOI] [PubMed] [Google Scholar]
  17. O'Brien P. C. The appropriateness of analysis of variance and multiple-comparison procedures. Biometrics. 1983 Sep;39(3):787–794. [PubMed] [Google Scholar]
  18. Polinsky R. J. Clinical autonomic neuropharmacology. Neurol Clin. 1990 Feb;8(1):77–92. [PubMed] [Google Scholar]
  19. Robertson D., Davis T. L. Recent advances in the treatment of orthostatic hypotension. Neurology. 1995 Apr;45(4 Suppl 5):S26–S32. [PubMed] [Google Scholar]
  20. Rudas L., Crossman A. A., Morillo C. A., Halliwill J. R., Tahvanainen K. U., Kuusela T. A., Eckberg D. L. Human sympathetic and vagal baroreflex responses to sequential nitroprusside and phenylephrine. Am J Physiol. 1999 May;276(5 Pt 2):H1691–H1698. doi: 10.1152/ajpheart.1999.276.5.h1691. [DOI] [PubMed] [Google Scholar]
  21. Sadjadpour K. Pyridostigmine bromide and constipation in Parkinson's disease. JAMA. 1983 Mar 4;249(9):1148–1148. [PubMed] [Google Scholar]
  22. Shannon J., Jordan J., Costa F., Robertson R. M., Biaggioni I. The hypertension of autonomic failure and its treatment. Hypertension. 1997 Nov;30(5):1062–1067. doi: 10.1161/01.hyp.30.5.1062. [DOI] [PubMed] [Google Scholar]
  23. Smit A. A., Halliwill J. R., Low P. A., Wieling W. Pathophysiological basis of orthostatic hypotension in autonomic failure. J Physiol. 1999 Aug 15;519(Pt 1):1–10. doi: 10.1111/j.1469-7793.1999.0001o.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Stein R. D., Backman S. B., Collier B., Polosa C. Bradycardia produced by pyridostigmine and physostigmine. Can J Anaesth. 1997 Dec;44(12):1286–1292. doi: 10.1007/BF03012778. [DOI] [PubMed] [Google Scholar]
  25. Thompson J. M., Jennings G. L., Chin J. P., Esler M. D. Measurement of human sympathetic nervous responses to stressors by microneurography. J Auton Nerv Syst. 1994 Nov;49(3):277–281. doi: 10.1016/0165-1838(94)90174-0. [DOI] [PubMed] [Google Scholar]
  26. Wright R. A., Kaufmann H. C., Perera R., Opfer-Gehrking T. L., McElligott M. A., Sheng K. N., Low P. A. A double-blind, dose-response study of midodrine in neurogenic orthostatic hypotension. Neurology. 1998 Jul;51(1):120–124. doi: 10.1212/wnl.51.1.120. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES