Inhibitory Effect of α1 Receptor Antagonists on Paclitaxel-Induced Peripheral Neuropathy in a Rodent Model and...

Area of Science:

• Neuroscience
• Pharmacology
• Oncology

Background:

• Paclitaxel is a vital chemotherapy drug for several cancers.
• Paclitaxel frequently causes peripheral neuropathy, a debilitating side effect.
• Current prophylactic treatments for paclitaxel-induced peripheral neuropathy are insufficient.

Purpose of the Study:

• To investigate the potential of alpha1-receptor antagonists in preventing paclitaxel-induced peripheral neuropathy.
• To evaluate the efficacy of doxazosin and tamsulosin in preclinical models and real-world data.

Main Methods:

• Utilized Sprague-Dawley rat models to assess paclitaxel-induced peripheral neuropathy.
• Administered doxazosin and tamsulosin to evaluate their neuroprotective effects.
• Analyzed the Food and Drug Administration Adverse Event Reporting System (FAERS) database for real-world evidence.

Main Results:

• Repeated administration of doxazosin or tamsulosin significantly reduced paclitaxel's impact on nerve response thresholds in rats.
• These alpha1-receptor antagonists markedly suppressed axonal degeneration and myelopathy in sciatic nerve tissues.
• FAERS data indicated a significantly lower reporting rate of paclitaxel-related peripheral neuropathy in patients using alpha1 inhibitors.

Conclusions:

• Doxazosin and tamsulosin demonstrate potential as prophylactic agents against paclitaxel-induced peripheral neuropathy.
• The neuroprotective mechanism appears to involve the suppression of neurodegeneration, specifically axonal damage and myelopathy.
• Further clinical investigation is warranted to confirm the therapeutic utility of alpha1-receptor antagonists in managing chemotherapy-induced peripheral neuropathy.