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Cited by 83Blood Pressure and Hypertension StudiesReceptor Mechanisms and SignalingHeart Rate Variability and Autonomic Control

The hypotensive activity and side effects of methyldopa, clonidine, and guanfacine

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van Zwieten, P A, Thoolen, M J, Timmermans, P B·1984·Hypertension
DOI 10.1161/01.hyp.6.5_pt_2.ii28
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Abstract

Clonidine (Catapres, Catapresan), guanfacine (Estulic), and methyldopa (Aldomet) are the prototypes of centrally acting antihypertensive drugs. Clonidine and guanfacine are lipophilic drugs that readily penetrate into the brain, where they stimulate alpha-adrenergic receptors in the pontomedullary region. The stimulation of these central alpha-adrenergic receptors has been shown to activate an inhibiting neuron, which causes a reduction of peripheral sympathetic tone and a subsequent fall in arterial blood pressure and heart rate. Both a centrally initiated reduction of vagus reflex activity and the activation of presynaptic alpha 2-adrenergic blocking agents in the heart may contribute to the bradycardia. Studies indicate that methyldopa also penetrates into the brain, where it is converted into alpha-methylnorepinephrine. This amine may stimulate the same central alpha-adrenergic receptors as those activated by clonidine, which will result in a hypotensive effect. Possibly, alpha-methyldopamine might also play a role. Accordingly, the modes of action of clonidine and alpha-methyldopa probably are very similar at a basic level. The central adrenergic receptors probably are located postsynaptically. Their receptor demand corresponds more closely to that of the alpha 2-subtype. Central alpha 1-adrenergic receptors might possibly play a part in the modulation of vagally induced baroreflex bradycardia. A discussion on the pharmacological basis of the side effects of the centrally acting antihypertensives has been limited to those adverse reactions that are somehow related to alpha-adrenergic receptors. Sedation, a common side effect, appears to be mediated by central alpha 2-adrenergic receptors, at least in animal models.(ABSTRACT TRUNCATED AT 250 WORDS)

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  • Guanfacine has fewer CNS adverse effects than clonidine, such as sedation, headache, orthostatic hypotension and impotence, and a lower incidence of withdrawal symptoms such as high BP, headache, tremor, restlessness, and nausea (3% vs. 50-80% with clonidine).

    “Also, guanfacine has fewer CNS adverse effects than clonidine, such as sedation, headache, orthostatic hypotension and impotence,42,43 and a lower incidence of withdrawal symptoms such as high BP, headache, tremor, restlessness, and nausea (3% vs. 50–80% with clonidine).42,44–47”

    From Hyperadrenergic Postural Tachycardia Syndrome: Clinical Biomarkers and Response to Guanfacine (2024) · cites this paper as [46]

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Research works printed but not linked: 4

  1. Nijkamp FP. De Jong W. a-Methylnoradrenaline induced hy- potension and bradycardia after administration into the area of the nucleus tractussolitani. EurJ Pharmacol l975;32:36l-364
  2. Henning M. Van Zwieten PA. Central hypotensive action of a- methyldopa. J Pharm Pharmacol 1968;20:409-4l7 13
  3. Van Zwieten PA. Antihypertensive drugs with a central action. Prog Pharmacol 1975,1:1-66
  4. Struyker Boudier HAJ. Catecholamine receptors in nervous tissue [Dissertation]. The Netherlands, University of Nijme- gen, 1975

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Authors
van Zwieten, P. A., Thoolen, M. J., & Timmermans, P. B.
Venue
Hypertension
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
1984-09
Volume
6
Issue
5_pt_2
Pages
II28-33
ISSN
  • 0194-911X (ISSN-L)
  • 1524-4563
DOI
10.1161/01.hyp.6.5_pt_2.ii28
OpenAlex
W2098810848
Cited by
83
References
39
Citations by year
2024: 1 · 2023: 1 · 2022: 2 · 2020: 2 · 2019: 2 · 2017: 4 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 2 · 2012: 1
FWCI
0.59
Type
journal article
Language
en
Open access
Locations
  • Hypertension (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
Keywords
methyldopa, clonidine, guanfacine, alpha-adrenergic receptors, alpha2-adrenoceptors, alpha-methylnorepinephrine, alpha-methyldopamine, bradycardia, baroreflex, sedation, adverse drug reactions, hypotensive mechanism, sympathetic tone
MeSH terms
Animals, Antihypertensive Agents, Blood Pressure, Bradycardia, Brain, Clonidine, Guanidines, Humans, Methyldopa, Norepinephrine, Phenylacetates, Receptors, Adrenergic, alpha, Structure-Activity Relationship, Substance Withdrawal Syndrome, Synapses, Tissue Distribution, Guanfacine

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