Major Research Findings

Thioridazine is a phenothiazine derivative that has been used as an antipsychotic drug for many years. Recent studies have shown that thioridazine has potential antitumor effects, particularly against cancer stem cells. 7 , 9 , 6 , 5 Research has demonstrated that thioridazine can suppress the growth of various types of cancer cells, including colorectal cancer stem cells, gastric cancer cells, and lung cancer stem-like cells, by inducing apoptosis. 4 In addition, thioridazine has been shown to have anti-angiogenic effects by inhibiting the proliferation of endothelial cells and suppressing the signaling pathways involved in angiogenesis. 10

However, thioridazine also has the potential to cause cardiotoxicity, specifically QT interval prolongation. 8 Research has shown that the (+)-enantiomer of thioridazine is primarily responsible for this cardiotoxic effect. 11 Other studies have explored the effects of thioridazine on the central nervous system, showing its ability to influence the release of neurotransmitters like dopamine and acetylcholine. 12 , 19 , 16 Thioridazine also has sedative effects and may affect autonomic functions such as pupil constriction, blood pressure reduction, and decreased salivation. 1

Benefits and Risks

Benefit Summary

Thioridazine has shown promise as an antitumor agent, particularly against cancer stem cells, and has anti-angiogenic effects. This suggests potential applications in cancer treatment and potentially in managing angiogenesis-related conditions. 7 , 9 , 6 , 5 , 10

Risk Summary

Thioridazine carries a risk of cardiotoxicity, specifically QT interval prolongation. This can lead to serious heart rhythm problems. It also affects neurotransmitter release and can cause sedation, potentially impacting psychomotor function and activities requiring alertness. Additionally, it may influence autonomic functions, leading to pupil constriction, decreased blood pressure, and reduced salivation. 8 , 12 , 19 , 16 , 1

Comparison of Studies

Similarities in Studies

Multiple studies consistently indicate that thioridazine can suppress the growth of cancer cells and induce apoptosis. 7 , 9 , 6 , 5 Additionally, research suggests that thioridazine can influence the release of neurotransmitters. 12 , 19 , 16

Differences in Studies

Research findings on thioridazine's effects and mechanisms vary across studies. For instance, the (+)-enantiomer of thioridazine has been shown to have a more pronounced cardiotoxic effect than the (-)-enantiomer. 8 Furthermore, while some studies have demonstrated thioridazine's anti-angiogenic effects, others have not shown similar results. 10

Consistency and Contradictions in Results

Research reveals that thioridazine has a wide range of effects, including anticancer activity, neurotransmitter modulation, and cardiotoxicity. While some findings are consistent, contradictions also exist. Particularly, the cardiotoxic effect of thioridazine seems to be influenced by factors such as the enantiomer used and the method of administration. 8 Further research is needed to understand the complexities of thioridazine's effects and address these inconsistencies.

Considerations for Real-World Application

While thioridazine holds potential for treating cancer and potentially managing angiogenesis-related conditions, it's crucial to remember its significant cardiotoxicity. If thioridazine is considered for therapeutic use, careful monitoring of heart function and potential cardiac risks is necessary. Furthermore, thioridazine can influence neurotransmitter release and cause sedation, potentially affecting alertness and psychomotor abilities. It's vital to exercise caution when engaging in activities requiring mental focus and coordination while taking thioridazine. 8 , 12 , 19 , 16 , 1

Limitations of Current Research

Research on thioridazine is still ongoing, and there are limitations to our current understanding. Notably, human studies are relatively limited, and it's unclear how well results from animal experiments translate to human applications. Additionally, individual variations in response to thioridazine due to genetics, other medications, and overall health status may influence its effects. Therefore, careful consideration and consultation with a healthcare professional are essential before using thioridazine.

Future Research Directions

Further clinical trials in human populations are necessary to gain a more comprehensive understanding of thioridazine's effects and efficacy. Research aimed at elucidating thioridazine's mechanisms of action and developing safer drug formulations or therapies to mitigate its adverse effects is crucial. Additionally, studying the interactions between thioridazine and other medications is important to ensure safe and effective therapeutic use.

Conclusion

Thioridazine holds promising potential as an antitumor agent and for managing angiogenesis, but it also carries a significant risk of cardiotoxicity. While research is ongoing, current findings suggest that thioridazine should be used with caution and only under the guidance of a qualified healthcare professional. Further research is needed to fully understand the complexities of thioridazine's effects, address existing knowledge gaps, and develop safer treatment strategies for its therapeutic application.