#61

This paper is open access

https://onlinelibrary.wiley.com/doi/10.1111/cpr.13764

They were using Palmitic Acid to reduce the MMP and terazosin restored it. I am not sure that this can be carried forward to fixing a flawed mtDNA or the effects of it.

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#62

Yes that’s the one I cited here: Terazosin / doxazosin / alfuzosin may protect against dementia with Lewy bodies - #59 by adssx

But the one I don’t have access to and that looked at MMP is this one: Terazosin / doxazosin / alfuzosin may protect against dementia with Lewy bodies - #49 by adssx

And yes you’re right, we don’t know if that’s transferable to damage from say aging.

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#63

If it were really so simple to just increase ATP to prevent dementia, then good old creatine monohydrate might be beneficial.

I looked for information on exercise and Terrazosin, and I was surprised to find that Terrazosin is thought to have a negative effect on performance in spite of the enhanced glycolysis.

#64

Bad news? Network Analysis and Machine Learning for Signal Detection and Prioritization Using Electronic Healthcare Records and Administrative Databases: A Proof of Concept in Drug-Induced Acute Myocardial Infarction 2025

Among the remaining signals, 80 were prioritized, and five emerged as the highest priority: terazosin, tamsulosin, allopurinol, esomeprazole, and omeprazole.
Terazosin and tamsulosin, both alpha-1 adrenergic antagonists primarily used for treating benign prostatic hyperplasia and hypertension, have been associated with adverse cardiovascular effects. These drugs lower blood pressure by causing vasodilation; however, they can also lead to postural hypotension and reflex tachycardia. The cardiovascular stress induced by these side effects may increase the risk of AMI, particularly in older patients or those with pre-existing cardiovascular conditions.

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#65

Cross-posting:

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#66

I didn’t know there was a trial of terazosin for ALS in Oxford. “Participants will take up to 10mg oral terazosin daily for up to 6 months.”

“Overall study end date 31/03/2025”
“Intention to publish date 31/03/2026”

One year to publish the results
 Academia is a disgrace.

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#67

Modulation of neuronal α1-adrenergic receptor reduces tauopathy and neuroinflammation by inhibiting the STING/NF-ÎșB/NLRP3 signaling pathway in Alzheimer’s disease mice 2025

:warning: Preprint + China + Mice :warning:

ADRA1 critically mediates tauopathy and neuroinflammation through STING/NF-ÎșB/NLRP3 signaling. These results identify ADRA1 as a promising therapeutic target for AD prevention and treatment.

Consistently, pretreatment with Terazosin or AMD3100 suppressed AÎČ42-mediated elevations in p-Taus396, p-Tau202/205, p-Tau231 and total Tau5 levels, along with reduced activation of the NF-ÎșB pathway (p-NF-ÎșB p65/NF-ÎșB p65) and NLRP3 inflammasome components (NLRP3, caspase-1, cleaved caspase-1, IL-1ÎČ, and IL-18)
Notably, Terazosin and AMD3100 also suppressed AÎČ42-induced ROS elevation in SH-SY5Y cells.
The progression of AD is marked by two synergistic pathological drivers—reactive gliosis and maladaptive cytokine release—which collectively establish neuroinflammatory suppression as a non-negotiable therapeutic priority. Preclinical studies demonstrate that ADRA1 antagonist Terazosin reduces hippocampal and cortical GFAP/CD68 expression in APP/PS1 mice, whereas ADRA1 agonist phenylephrine enhances astrocytic IL-6 production. Our findings align with this paradigm, showing that neuronal ADRA1 overexpression in WT mice elevates hippocampal GFAP, Iba-1, and inflammatory cytokine levels. Notably, IL-6—a key mediator amplified in this process—activates the STAT3/cGAS/STING signaling pathway in glial cells to propagate neuroinflammation. This suggests that IL-6 upregulation induced by neuronal ADRA1 dysregulation may initiate a self-perpetuating cycle of glial activation and neuroinflammatory exacerbation via STAT3/cGAS/STING signaling.

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#68

Antihypertensive Drug Use and COVID-19 Disease Severity in Hospitalized US Veterans: A Retrospective Cohort Study 2025

After adjusting for the aforementioned potential confounding variates, CCBs (HR: 1.09, 95% CI (1.03–1.16), p = 0.002) were independently associated with an increased risk of mechanical ventilation. In contrast, ACEI (HR: 0.90, 95% CI (0.85–0.95), p < 0.001), alpha blockers (HR: 0.92, 95% CI (0.87–0.97), p = 0.001), and CCB (HR: 0.93, 95% CI (0.88–0.98), p = 0.006) were independently associated with a decreased risk for mortality (Table 2).
Interestingly, alpha blockers were associated with a protective function against death. According to the JNC-8 recommendations, alpha blockers are a 3rd-line antihypertensive treatment prescribed when hypertension is unable to be controlled by first or second-line treatments [27]. A possible mechanism for the protective effect of alpha blockers may result from their ability to reduce left ventricular hypertrophy, an independent risk factor for cardiovascular mortality and morbidity, and improve glomerular filtration rate, reducing kidney damage [35]. Given the diversity, complexity, and frequency of confounding comorbidities in hypertensive patients, prospective randomized control or propensity-matched studies are needed to study the effects of alpha blockers on COVID-19 severity.

#69

The massive issue with alpha-1 blockers is their potential cardiotoxicity


α1-Adrenergic receptors prevent a maladaptive cardiac response to pressure overload 2006

These results suggest that the adverse cardiac effects of α1-antagonists in clinical trials are due to loss of α1-signaling in myocytes, emphasizing concern about clinical use of α1-antagonists, and point to a revised perspective on sympathetic activation in heart failure.
One arm of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) in hypertension tested the α1-antagonist doxazosin versus the diuretic chlorthalidone in 24,335 men and women with cardiac risk factors (5). This arm of the trial was stopped prematurely, because doxazosin doubled the incidence of heart failure, and further detailed analyses indicated a doxazosin effect to increase heart failure that was not seen with other antihypertensive medications (5–8). Similarly, in the Vasodilator–Heart Failure Trials (V-HeFT), the α1-antagonist prazosin did not improve survival as did other vasodilators and even tended to increase mortality (9). Doxazosin and prazosin are piperazinyl quinazolines, which at high doses can cause apoptosis in heart and other tissues independent of α1-ARs (10, 11), and also have relatively high affinity for α2-AR subtypes B and C (12, 13).

On the other hand: Unraveling the relationships between alpha- and beta-adrenergic modulation and the risk of heart failure 2023

Lower α1A or ß1 activity was associated with reduced HF risk: odds ratio (OR) 0.83 (95% CI 0.74–0.93, P = 0.001) and 0.95 (95% CI 0.93–0.97, P = 8 × 10−6).
This study provides genetic evidence that α1A or ß1 receptor inhibition will likely decrease HF risk, while lower α2B activity may increase this risk. Genetic variant analysis can assist with drug development for HF prevention.
There are contradictory data on the role of α1 blockers in HF. Doxazosin and prazosin were associated with an increased risk of HF in several studies, including the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT) and another trial comparing doxazosin to chlorthalidone (3, 5, 42). However, no direct comparison between α1 blockers and placebo in a large trial is available. On the contrary, non-specific α1 blockers were recently associated with an improvement in death and rehospitalization for HF, and specific α1A blockers with a neutral effect in a large HF cohort (6).

:man_shrugging:

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