Therapeutics

Carvedilol

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Overview

Name: Carvedilol
Synonyms: Coreg, Artist , Aucardic, Dilatrend, Kredex
Chemical Name: 1-(Carbazol-4-yloxy)-3-[[2-(o-methoxyphenoxy)ethyl]amino]-2-propanol
Therapy Type: Small Molecule
Target Type: Unknown
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 4)
Company: Procter & Gamble
Approved for: Hypertension, heart failure, angina pectoris

Background

Carvedilol phosphate is a non-selective α/β-adrenergic receptor antagonist and vasodilator. This drug has been available in the United States and many other countries since the mid-1990s. It is widely prescribed to treat high blood pressure and other cardiovascular problems, and is available as an extended-release capsule. Its side effects include slowness of movement, dizziness, fatigue, headache, and nausea. 

The rationale for evaluating it in Alzheimer's disease grew out of several lines of research suggesting that neurovascular dysfunction contributes to age-related dementia, that antihypertensive treatment in incident Alzheimer's may slow further cognitive decline, and that carvedilol improves synaptic transmission and amyloid-related and cogntive outcomes in mouse models of Alzheimer's disease (Dunn and Nelson, 2014; Rosenberg et al., 2008; Wang et al., 2011). Meta-analysis of the epidemiological literature has shown hypertension in mid-life—but not in late life—to increase risk for dementia (see AlzRisk).

Findings

Carvedilol is being evaluated in an investigator-initiated study at the Alzheimer's Disease Research Center of Johns Hopkins University Medical Center. This six-month, 50-patient trial aims to determine whether daily treatment with 25 mg carvedilol—the half-maximum dose used in clinical practice—improves memory in Alzheimer's disease compared to placebo. The study enrolls people with mild AD, and measures episodic memory with the Hopkins Verbal Learning Test, as well as cerebrospinal fluid levels of Aβ oligomers. The trial is set to run until June 2015. For details see clinicaltrials.gov

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References

Paper Citations

  1. . Neurovascular signaling in the brain and the pathological consequences of hypertension. Am J Physiol Heart Circ Physiol. 2014 Jan 1;306(1):H1-14. Epub 2013 Oct 25 PubMed.
  2. . Effects of cardiovascular medications on rate of functional decline in Alzheimer disease. Am J Geriatr Psychiatry. 2008 Nov;16(11):883-92. PubMed.
  3. . Carvedilol as a potential novel agent for the treatment of Alzheimer's disease. Neurobiol Aging. 2011 Dec;32(12):2321.e1-12. PubMed.

External Citations

  1. clinicaltrials.gov
  2. AlzRisk

Further Reading

Papers

  1. . Roles of β-adrenergic receptors in Alzheimer's disease: implications for novel therapeutics. Brain Res Bull. 2011 Feb 1;84(2):111-7. PubMed.
  2. . Less Alzheimer disease neuropathology in medicated hypertensive than nonhypertensive persons. Neurology. 2009 May 19;72(20):1720-6. PubMed.