Terazosin/doxazosin/alfuzosin may protect against dementia with Lewy bodies

#1

We find an association in men who are taking Tz/Dz/Az and a lower hazard of DLB compared with similar men taking other medications. When combined with the literature of Tz/Dz/Az on Parkinson disease, our findings suggest that glycolysis-enhancing drugs may be broadly protective in neurodegenerative synucleinopathies. A future randomized trial is required to assess these associations for causality.

The UI researchers think that a specific side effect of the drugs targets a biological flaw shared by DLB and Parkinson’s disease, as well as other neurodegenerative diseases, raising the possibility that they may have broad potential for treating a wide range of neurodegenerative conditions.
For the new study, the UI researchers used a large database of patient information to identify more than 643,000 men with no history of DLB who were newly starting one of six drugs used to treat benign prostatic hyperplasia (enlarged prostate).
Three of the drugs, terazosin, doxazosin, and alfuzosin (Tz/Dz/Az), have an unexpected side effect; they can boost energy production in brain cells. Preclinical studies suggest that this ability may help slow or prevent neurodegenerative diseases like PD and DLB.
The other drugs, tamsulosin and two 5-alpha-reductase inhibitors (5ARIs) called finasteride and dutasteride, do not enhance energy production in the brain and therefore provide a good comparison to test the effect of the Tz/Dz/Az drugs.

In addition to BPH (benign prostatic hyperplasia), alpha-1 blockers like terazosin are also used in resistant hypertension (after ARB + DHP CCB + Thiazide-like at max dose failed to reach BP goals).

Could low-dose terazosin be interesting for neuroprotection in men with elevated BP @DrFraser?

Half of males above 50 suffer from BPH, so should they all take terazosin rather than finasteride?

Terazosin 1 mg also potentially useful for hyperhidrosis: Effect of terazosin on sweating in patients with major depressive disorder receiving sertraline: a randomized controlled trial 2012

Five ongoing trials, results expected between 2024 and 2026:

  • Terazosin Effect on Cardiac Changes in Early Parkinson’s Disease
  • Terazosin for Dementia With Lewy Bodies
  • Motor Function Efficacy of Pharmacological Treatments Targeting Energy Metabolism, in Parkinson’s Patients
  • Terazosin and Parkinson’s Disease Extension Study
  • A Randomized Controlled Trial of Doxazosin for Nightmares, Sleep Disturbance, and Non-Nightmare Clinical Symptoms in PTSD

I sponsored terazosin in Ora Biomedical MMC and it failed btw:

image
image1754Ă—374 42 KB

2 Likes
#2

The alpha blockers, like terazosin have a few side effects, and I wonder how much of this is dose dependent, as dosing is 1-10 mg. Postural hypotension, hypotension, tachycardia, somnolence, nervousness are among the common ones. If it was good at 1 mg … probably low rate of side effects … at 10 mg … might find a few with head injuries from passing out with standing.

1 Like
#3

The terazosin DDD for BPH is 5 mg, so we can assume it was the dose used by men in the above study. So 5 mg might already be neuroprotective. Can we go even lower? The trials are using 2 to 10 mg (as the target dose), so we’ll soon know. Also: what about low-dose but long-term accumulation? Could 1 mg per day for 10 years be as good as (if not better than) 10 mg per day for one year in terms of neuroprotection?

1 Like