#41

To my surprise, you are both right! Although low dose tadalafil was FDA approved for BPH in 2011, the approval was based on clinical studies that demonstrated the efficacy of tadalafil in improving the symptoms of BPH… I am going to try 2,5mg tadalafil and 1 mg terazosin in a few week, after I return from holiday

#42

I think terazosin is also only symptomatic. In some countries they don’t sell 1 mg so you have to buy 5 mg and cut it. Also, tadalafil can reinforce the BP lowering of terazosin (or vice versa?) so you should be cautious: https://www.drugs.com/drug-interactions/cialis-with-terazosin-2144-1395-2159-0.html

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#43

Thanks for the advice. I live in Belgium and I can get generic 2mg tablets that are splittable in 2. I will start with 0,5 mg terazosin before sleep and then check my BP in the morning

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#44

Please let me know how it goes @Ludovic!

I tried 1 mg twice (split 2 mg) and noticed great vivid dreams + stronger morning erection. Interestingly prazosin is used to treat nightmares in PTSD. Some people report the same thing here: https://www.reddit.com/r/zosin/new/

I also found some papers and anecdotal evidence about reduced sweating in people with hyperhidrosis.

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#45

It would seem like Alfuzosin might be the kindest in regard to postural hypotension and lowering BP. On the standard 10 mg ER tablet, it looks like average range of lowering systolic BP is just 2-4 mmHg.

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#46

Finding replicated by Ora Biomedical: Ora Biomedical Million Molecule Challenge Results - #229 by adssx

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#47

No neuroprotection found here (but did they didn’t include the latest studies published in 2024): Association Between Alpha-1 Adrenoreceptor Antagonist Use and Cognitive Impairment: A Systematic Review 2024

Our systematic review did not show a convincing causal association between α1-AR antagonists, including tamsulosin, and cognitive dysfunction. Considering the existing literature, it is appropriate to use α1-AR antagonists without concern for cognitive dysfunction. Future research, through robust study designs considering the multifactorial nature of cognitive dysfunction, is required to further evaluate this association.

#48

Terazosin, a repurposed GPR119 agonist, ameliorates mitophagy and β-cell function in NAFPD by inhibiting MST1-Foxo3a signalling pathway 2024

Terazosin administration improved high blood glucose, obesity, and impaired pancreatic β-cell function in NAFPD mice. It inhibited the upregulation of MST1-Foxo3a expression in pancreatic tissue and enhanced damaged mitophagy clearance, restoring autophagic flux, and improving mitochondrial quantity and structure in β-cells.
Terazosin could be considered a priority treatment for patients with concomitant NAFPD and hypertension.

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#49

It’s in flies but I find this study quite fun: Activation of glycolysis alleviates mitochondrial impairments caused by social isolation in Drosophila 2024

Social isolation reduces mitochondrial function; Pgk activation rescues this deficit.
Social isolation (SI) in humans can lead to various psychological and physical abnormalities. However, the molecular mechanisms and potential drug treatments for this illness are not well understood. Drosophila, a social organism, exhibits distinct behavioral defects under SI conditions, such as reduced sleep and loss of sugar intake preference. By examining the transcriptional profiles of SI flies, we discovered significant impacts on metabolic pathways. Notably, serotonin (5-HT) levels were reduced in the brains of SI flies. Treatment with 5-HT reversed the behavioral defects in SI flies. 5-HT is known to regulate mitochondrial synthesis in mouse brain, and we found it also enhances mitochondrial biogenesis in flies. Further investigation revealed that the 5-HT7 receptor subtype was involved in SI behavior. To activate mitochondrial metabolism, we overexpressed phosphoglycerate kinase (Pgk), an enzyme in the glycolytic pathway, in neurons. This overexpression rescued the behavioral defects in SI flies. Additionally, terazosin, an alpha-1 adrenergic receptor antagonist known to activate Pgk, produced a similar rescue effect. Our study elucidates a key principle of SI-induced psychological damage and proposes a drug targeting strategy for future validation.

#50

Repurposing FDA-approved drugs targeting FZD10 in nasopharyngeal carcinoma: insights from molecular dynamics simulations and experimental validation 2024

Doxazosin can induce apoptosis in various cancer cell types, including prostate cancer cells, neuroblastoma cells, breast cancer cell through EGFR and NF-κB pathway. It also sensitizes cancer cells to Osimertinib, an anticancer drug.

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#51

Target the Heart: a new axis of Alzheimer’s disease prevention 2025

:warning: Preprint :warning:

Cyclosporine A and other calcineurin inhibitors have been identified as prospective treatments for preventing Alzheimer’s disease. Utilizing a neural network model, Z-LaP Tracker, we previously found that calcineurin inhibitors elicit a unique behavioral profile in zebrafish larvae characterized by increased activity, acoustic hyperexcitability, and reduced visually guided behaviors. Screening a large library of FDA-approved drugs using Z-LaP Tracker revealed a cluster of 65 drugs demonstrating a cyclosporine A-like behavioral profile. 14 of these drugs were heart medications, including angiotensin receptor blockers, beta-blockers, alpha-adrenergic receptor antagonists, and a statin. This suggests some heart medications may be effective in preventing or ameliorating Alzheimer’s disease pathology. Other studies have shown that many of these 14 drugs directly or indirectly inhibit the calcineurin-NFAT pathway, alike cyclosporine A. Dual administration of the heart medications with cyclosporine A in Z-LaP Tracker revealed synergistic effects: lower doses of each heart medication could be delivered in conjunction with a lower dose of cyclosporine A to evoke a similar or larger behavioral effect than higher doses of each drug independently. This indicates that co-administering a low dose of cyclosporine A with select cardiac drugs could be a potentially effective treatment strategy for Alzheimer’s disease and cardiovascular dysfunction, while mitigating side effects associated with higher doses of cyclosporine A. Given that heart disease precedes Alzheimer’s disease in many patients, physicians may be able to create a treatment regimen that simultaneously addresses both conditions. Our results suggest that cyclosporine A combined with simvastatin, irbesartan, cilostazol, doxazosin, or nebivolol are the most promising candidates for future exploration.

The usual suspects:

Upon comparison with two small-molecule libraries, Tocriscreen FDA-approved Drugs Library and Cayman Chemical FDA-Approved Drugs Screening Library , we identified 14 FDA-approved heart therapeutics that prompted CsA-like behavioral profiles: irbesartan, losartan, eprosartan, telmisartan, doxazosin, prazosin, nebivolol, carvedilol, simvastatin, droperidol, trifluoperazine, mirtazapine, calcifediol, and cilostazol .

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#52

I am highly curious about the various zozins now. It is claimed that they increase ATP availability. ATP is mitochondria fuel–well, it is just plain cell fuel for everything. I am using Flomax at present, but perhaps I should consider one of the zozins instead. More ATP for the muscles would be great for workouts, and my brain needs all the help it can get. I wonder what the downsides of the zozins might be?

#53

Do you have a reference to this?

#54

Perhaps I am misunderstanding the paper bigly as the president might say.

“α-1 adrenergic receptor antagonists that also bind to and activate a key adenosine triphosphate (ATP)–producing enzyme in glycolysis. It is hypothesized that the increase in energy availability in the brain may slow or prevent neurodegeneration,”

Is this saying that available ATP is improved for all cells and tissues? That seems way too easy.

#55

A pilot dose-finding study of Terazosin in humans

Our results indicated that a 5 mg/day dose of TZ significantly increased whole blood ATP levels and reduced global cerebral 18F-FDG PET uptake without significant side effects or orthostatic hypotension. These effects were consistent across sexes. Higher doses did not result in additional benefits and showed a potential biphasic dose-response.

I tried terazosin 1 mg twice for a couple of days. I took it at bedtime. The first day I literally woke up and started to do push-ups right after. Never done that in my life. I had a lot of energy. The energy boost was less intense the following days but still there. Unfortunately, terazosin gave me a bit of orthostatic hypotension so I stopped. I think it might be worth trying again as trials seem to show that the hypotension can disappear after some time.

@Ray1: based on all the papers, tamsulosin (Flomax) might not be ideal for the brain.

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#56

Homeostasis is an issue that has effects. If the cells find there is what they determine as too much energy then they wind things back by possibly fusing mitochondria.

The complex area is that the cells ordinarily cannot actually make the mitochondria more efficient (other than through mitophagy) hence although they can increase ATP availability and reduce it they cannot change the ratio between ATP and acetyl-CoA other than by increasing mitochondrial efficiency.

Hence an intervention that increases ATP availability without increasing mitochondrial efficiency is likely to be knocked back. I will read the link.

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#57

It seems that terazosin, in addition to increasing ATP, also improve mitochondrial function (see the various papers I posted in this thread).

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#58

Scanning that paper, however, its primary affect is on glycolysis and hence it would not increase the Mitochondrial membrane potential.

Hence although it would increase the efficiency by which glucose is converted to acetyl-CoA it depends whether you see that as part of the mitochondrial function (it occurs in the cytosol).

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#59

Simultaneous terazosin intervention led to an increased ratio of red fluorescence aggregates to green fluorescence monomers, effectively restoring the membrane potential (Figure 5A, B).
Terazosin reversed the decline in mitochondrial membrane potential caused by PA. (A)

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#60

This paper also looked at MMP but I don’t have access to the full text.