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Article

The Antidepressant Duloxetine Inhibits Platelet Function and Protects against Thrombosis

by
Patricia A. Lozano
1,
Ahmed B. Alarabi
1,
Sarah E. Garcia
2,
Erica T. Boakye
2,
Hendreta T. Kingbong
2,
Elie Naddour
2,
Daniel Villalobos-García
3,
Precious Badejo
3,
Medhat S. El-Halawany
3,
Fadi T. Khasawneh
3,* and
Fatima Z. Alshbool
1,*
1
Department of Pharmacy Practice, Irma Lerma Rangel College of Pharmacy, Texas A&M University, Kingsville, TX 78363, USA
2
School of Pharmacy, The University of Texas at El Paso, El Paso, TX 79902, USA
3
Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University, Kingsville, TX 78363, USA
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2022, 23(5), 2587; https://doi.org/10.3390/ijms23052587
Submission received: 14 February 2022 / Revised: 23 February 2022 / Accepted: 23 February 2022 / Published: 26 February 2022
(This article belongs to the Special Issue Drug Discovery and Novel Platelet Signaling in Thrombogenesis)
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Abstract

While cardiovascular disease (CVD) is the leading cause of death, major depressive disorder (MDD) is the primary cause of disability, affecting more than 300 million people worldwide. Interestingly, there is evidence that CVD is more prevalent in people with MDD. It is well established that neurotransmitters, namely serotonin and norepinephrine, are involved in the biochemical mechanisms of MDD, and consequently, drugs targeting serotonin-norepinephrine reuptake, such as duloxetine, are commonly prescribed for MDD. In this connection, serotonin and norepinephrine are also known to play critical roles in primary hemostasis. Based on these considerations, we investigated if duloxetine can be repurposed as an antiplatelet medication. Our results-using human and/or mouse platelets show that duloxetine dose-dependently inhibited agonist-induced platelet aggregation, compared to the vehicle control. Furthermore, it also blocked agonist-induced dense and α-granule secretion, integrin αIIbβ3 activation, phosphatidylserine expression, and clot retraction. Moreover duloxetine-treated mice had a significantly prolonged occlusion time. Finally, duloxetine was also found to impair hemostasis. Collectively, our data indicate that the antidepressant duloxetine, which is a serotonin-norepinephrine antagonist, exerts antiplatelet and thromboprotective effects and inhibits hemostasis. Consequently, duloxetine, or a rationally designed derivative, presents potential benefits in the context of CVD, including that associated with MDD.
Keywords: platelet; thrombosis; hemostasis; MDD; CVD; drug repurposing platelet; thrombosis; hemostasis; MDD; CVD; drug repurposing

Share and Cite

MDPI and ACS Style

Lozano, P.A.; Alarabi, A.B.; Garcia, S.E.; Boakye, E.T.; Kingbong, H.T.; Naddour, E.; Villalobos-García, D.; Badejo, P.; El-Halawany, M.S.; Khasawneh, F.T.; et al. The Antidepressant Duloxetine Inhibits Platelet Function and Protects against Thrombosis. Int. J. Mol. Sci. 2022, 23, 2587. https://doi.org/10.3390/ijms23052587

AMA Style

Lozano PA, Alarabi AB, Garcia SE, Boakye ET, Kingbong HT, Naddour E, Villalobos-García D, Badejo P, El-Halawany MS, Khasawneh FT, et al. The Antidepressant Duloxetine Inhibits Platelet Function and Protects against Thrombosis. International Journal of Molecular Sciences. 2022; 23(5):2587. https://doi.org/10.3390/ijms23052587

Chicago/Turabian Style

Lozano, Patricia A., Ahmed B. Alarabi, Sarah E. Garcia, Erica T. Boakye, Hendreta T. Kingbong, Elie Naddour, Daniel Villalobos-García, Precious Badejo, Medhat S. El-Halawany, Fadi T. Khasawneh, and et al. 2022. "The Antidepressant Duloxetine Inhibits Platelet Function and Protects against Thrombosis" International Journal of Molecular Sciences 23, no. 5: 2587. https://doi.org/10.3390/ijms23052587

APA Style

Lozano, P. A., Alarabi, A. B., Garcia, S. E., Boakye, E. T., Kingbong, H. T., Naddour, E., Villalobos-García, D., Badejo, P., El-Halawany, M. S., Khasawneh, F. T., & Alshbool, F. Z. (2022). The Antidepressant Duloxetine Inhibits Platelet Function and Protects against Thrombosis. International Journal of Molecular Sciences, 23(5), 2587. https://doi.org/10.3390/ijms23052587

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