The Potential Role of the Serotonin Transporter as a Drug Target against Parasitic Infections: A Scoping Review of the Literature

Background: Several in vitro and in vivo biological activities of serotonin, 5- hydroxytryptamine (5-HT), as a bioactive molecule, and its transporter (5-HT-Tr) were evaluated in parasitic infections. Objective: Herein, the roles of 5-HT and 5-HTR in helminths and protozoan infections with medical and veterinary importance are reviewed. Methods: We searched information in 4 main databases and reviewed published literature about the serotonin transporter's role as a promising therapeutic target against pathogenic parasitic infections between 2000 and 2021. Results: Based on recent investigations, 5-HT and 5-HT-Tr play various roles in parasite infections, including biological function, metabolic activity, organism motility, parasite survival, and immune response modulation. Moreover, some of the 5-HT-TR in Schistosoma mansoni showed an excess of favorite substrates for biogenic amine 5-HT compared to their mammalian hosts. Furthermore, the main neuronal protein related to the G protein-coupled receptor (GPCR) was identified in S. mansoni and Echinococcus granulosus, playing main roles in these parasites. In addition, 5-HT increased in toxoplasmosis, giardiasis, and Chagas disease. On the other hand, in Plasmodium spp., different forms of targeted 5-HTR stimulate Ca²⁺ release, intracellular inositol triphosphate (ITP), cAMP, and protein kinase A (PKA) activity. Conclusion: This review summarized the several functional roles of the 5-HT and the importance of the 5-HT-TR as a drug target with minimal harm to the host to fight against helminths and protozoan infections. Hopefully, this review will shed light on research regarding serotonin transporter-based therapies as a potential drug target soon.