Prazosin

[PCaWarrior]

1 mg BID reduced my BP from around 140/85 to about 120/70. This is a lower dose than the minimum standard dose (1 mg TID) so perhaps BAT, exercise, or diet had something to do with the BP decrease. Some guys on this site are taking Prazosin.

Prazosin

1. Mechanisms of Action

• α1-Adrenoceptor Antagonism: Prazosin is primarily known as an α1-adrenoceptor antagonist, commonly used to treat hypertension and benign prostatic hyperplasia by relaxing vascular smooth muscles.

• Induction of Apoptosis: Prazosin has been shown to induce apoptosis in prostate cancer cell lines, including PC-3, DU-145, and LNCaP. This apoptotic effect is associated with the induction of DNA damage stress, leading to cell cycle arrest at the G2 checkpoint.

• Inhibition of PI3K/AKT/mTOR Pathway: Studies suggest that prazosin may suppress cancer progression by downregulating the activity of the PI3K/AKT/mTOR signaling pathway, which plays a crucial role in tumor cell proliferation, migration, invasion, and apoptosis.

2. Research & Studies

• In Vitro Studies:

o Prazosin has demonstrated antiproliferative activity superior to other α1-blockers, inducing G2 checkpoint arrest and subsequent apoptosis in prostate cancer cell lines.

o In glioblastoma cells, prazosin inhibited proliferation, migration, and invasion by downregulating the PI3K/AKT/mTOR signaling pathway, suggesting a potential mechanism applicable to prostate cancer.

• In Vivo Studies:

o Oral administration of prazosin significantly reduced tumor mass in PC-3-derived cancer xenografts in nude mice, indicating its potential as an antitumor agent.

• Retrospective Clinical Analysis:

o A pilot retrospective analysis suggested that prazosin may reduce the risk of prostate cancer recurrence and delay time to biochemical relapse, providing a basis for further clinical investigation.

3. Overall Quality of Evidence

• Preclinical Evidence: Rated B. In vitro and in vivo studies provide substantial evidence of prazosin's anticancer activity against prostate cancer cells.

• Clinical Evidence: Rated C. Limited clinical data, primarily from retrospective analyses, suggest potential benefits, but prospective clinical trials are necessary to establish efficacy.

4. Conclusion

Prazosin exhibits promising anticancer properties in preclinical studies, including induction of apoptosis and inhibition of key signaling pathways in prostate cancer cells. However, clinical evidence remains limited, necessitating further research to validate these findings.

5. Common Side Effects

Prazosin is generally well-tolerated but may cause side effects, including:

• Orthostatic Hypotension: A sudden drop in blood pressure upon standing, leading to dizziness or fainting.

• Nasal Congestion: Due to vasodilation effects.

• Fatigue: General feelings of tiredness or weakness.

Patients should consult healthcare providers to weigh the benefits and risks of prazosin therapy, especially when considering combination treatments.

6. References

1. Prazosin Displays Anticancer Activity against Human Prostate Cancers: pubmed.ncbi.nlm.nih.gov

2. Prazosin Inhibits the Proliferation, Migration, and Invasion of Glioblastoma Cells via the PI3K/AKT/mTOR Signaling Pathway: spandidos-publications.com

3. A Pilot Retrospective Analysis of Alpha-Blockers on Recurrence in Prostate Cancer: Nature

[Adendino]

Your contributions to this group are valuable and appreciated. Glad to see your posts again after a long hiatus.

[PCaWarrior in reply to Adendino]

Thanks. Divorce. Wife knew for a year and told me when she was leaving.

[MateoBeach]

Good summary on Prazosin. I am convinced the weight of evidence that it can slow PCa progression. Doxazosin has similar actions evidenced. Just those two. Doxazosin has longer half life for twice daily dosing. I take 2mg twice daily. Must be titrated individually and slowly. Excellent BP control and part of my mHSPC management regimen.

[PCaWarrior in reply to MateoBeach]

Thanks. I'll look for a little more confirmation and, if I get it, I'll switch to Doxa.

"Both doxazosin and prazosin are alpha‐1 adrenergic receptor blockers traditionally used for managing lower urinary tract symptoms in benign prostatic hyperplasia (BPH). However, some preclinical research has explored whether these quinazoline-based compounds might also exhibit anti-tumor properties in prostate cancer (PCa).

Key Comparisons:

• Mechanism & Anti-Tumor Potential:

 – Doxazosin: Has been investigated for its ability to induce apoptosis and inhibit angiogenesis in prostate cancer cell lines. Some studies suggest it may disrupt tumor microenvironments, although these findings remain largely experimental.

 – Prazosin: Also a quinazoline derivative, but there is less preclinical data supporting a direct anti-tumor effect compared to doxazosin.

• Pharmacokinetics:

 – Doxazosin: With a long half-life (approximately 22 hours), it provides a more sustained receptor blockade, which might be advantageous if anti-tumor effects require prolonged exposure.

 – Prazosin: Its shorter half-life (2–3 hours) results in a shorter duration of action, potentially limiting its efficacy if continuous exposure is needed for anti-tumor activity.

Quality of Evidence:

• Preclinical Evidence: Both drugs have been studied in vitro, with doxazosin generally showing more promising anti-tumor effects (mechanistic evidence is modest, around a B rating)."

[PCaWarrior in reply to MateoBeach]

Great. ChatGPT fell on it's face. I ran out of deep research minutes and am going to stop asking it stuff until I get more time.

"5. Comparative Summary: Doxazosin vs. Prazosin in Prostate Cancer

• Mechanistic Similarities:

Both doxazosin and prazosin share the primary mechanism of α₁-adrenoceptor blockade and have demonstrated potential pro-apoptotic and anti-proliferative effects in preclinical prostate cancer models. However, prazosin has slightly more supportive mechanistic and preclinical data compared to doxazosin.

• Evidence Base:

o Preclinical Data:

Prazosin’s in vitro and animal data are more robust (Grade B) than those for doxazosin (Grade B to C).

o Clinical Data:

For both agents, clinical evidence remains preliminary (Grade C). Larger, randomized controlled trials are needed to establish clear therapeutic roles in prostate cancer management.

• Established Clinical Uses:

Both are approved and widely used for hypertension and BPH, which is an advantage in managing prostate cancer patients who also experience cardiovascular or urinary issues.

• Side Effects:

The side effect profiles are similar, with orthostatic hypotension, headache, and fatigue being the most common. Their tolerability in cancer patients should be closely monitored, especially if used off-label for potential anti-cancer effects.

"

[PCaWarrior in reply to MateoBeach]

Wonderful. I guess 2 out of 3 is good? I have to do the research.

"Quality of Evidence:

Doxazosin:

Preclinical: Moderate to strong evidence from in vitro and animal studies.

Clinical: Limited; evidence quality is moderate to low due to the absence of large, controlled trials.

Prazosin:

Preclinical: Evidence exists but is less extensive and somewhat inconsistent.

Clinical: Sparse clinical data leads to a quality assessment of low to moderate.

Conclusion:

Both drugs exhibit promising anti-cancer effects in preclinical models; however, the evidence remains primarily experimental. Doxazosin appears to have a slightly more favorable and better-studied profile compared to prazosin. Nonetheless, neither drug has yet been validated by robust clinical trials in the context of prostate cancer, so their utility in this setting remains investigational."