Multiple system atrophy: using clinical pharmacology to reveal pathophysiology

Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society
Jens JordanI Biaggioni

Abstract

Despite similarities in their clinical presentation, patients with multiple system atrophy (MSA) have residual sympathetic tone and intact post-ganglionic noradrenergic fibers, whereas patients with pure autonomic failure (PAF) and Parkinson disease have efferent post-ganglionic autonomic denervation. These differences are apparent biochemically, as well as in neurophysiological testing, with near normal plasma norephrine in MSA but very low levels in PAF. These differences are also reflected in the response patients have to drugs that interact with the autonomic nervous system. For example, the ganglionic blocker trimethaphan reduces residual sympathetic tone and lowers blood pressure in MSA, but less so in PAF. Conversely, the α2-antagonist yohimbine produces a greater increase in blood pressure in MSA compared to PAF, although significant overlap exists. In normal subjects, the norepinephrine reuptake (NET) inhibitor atomoxetine has little effect on blood pressure because the peripheral effects of NET inhibition that result in noradrenergic vasoconstriction are counteracted by the increase in brain norepinephrine, which reduces sympathetic outflow (a clonidine-like effect). In patients with autonomic failure and intact perip...Continue Reading

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Citations

Oct 3, 2015·Expert Review of Cardiovascular Therapy·Pearl K JonesSatish R Raj
Sep 14, 2016·Journal of the American Society of Hypertension : JASH·Horacio KaufmannWilliam B White
Aug 20, 2017·Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society·Lucy Norcliffe-KaufmannVera Novak
Dec 25, 2016·Pharmacological Reviews·Italo Biaggioni
Apr 2, 2020·Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society·Chenjie Xia, Ronald B Postuma
Jan 31, 2020·Continuum : Lifelong Learning in Neurology·Jose-Alberto Palma, Horacio Kaufmann
Jul 18, 2017·Movement Disorders Clinical Practice·Jose-Alberto Palma, Horacio Kaufmann
Mar 7, 2018·Movement Disorders : Official Journal of the Movement Disorder Society·Jose-Alberto Palma, Horacio Kaufmann
Jan 4, 2018·Movement Disorders : Official Journal of the Movement Disorder Society·Elizabeth A CoonEduardo E Benarroch
Nov 18, 2019·Clinics in Geriatric Medicine·Jose-Alberto Palma, Horacio Kaufmann
Aug 21, 2021·Frontiers in Cardiovascular Medicine·Anna CalviAderville Cabassi

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