The antimalarial drug quinine interferes with serotonin biosynthesis and action

Islahudin, Farida, Tindall, Sarah M., Mellor, Ian R., Swift, Karen, Christensen, Hans E. M., Fone, Kevin C. F., Pleass, Richard ORCID: https://orcid.org/0000-0001-7438-8296, Ting, Kang-Nee and Avery, Simon V. (2014) 'The antimalarial drug quinine interferes with serotonin biosynthesis and action'. Scientific Reports, Vol 4, e3618.

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Abstract

The major antimalarial drug quinine perturbs uptake of the essential amino acid tryptophan, and patients with low plasma tryptophan are predisposed to adverse quinine reactions; symptoms of which are similar to indications of tryptophan depletion. As tryptophan is a precursor of the neurotransmitter serotonin (5-HT), here we test the hypothesis that quinine disrupts serotonin function. Quinine inhibited serotonin-induced proliferation of yeast as well as human (SHSY5Y) cells. One possible cause of this effect is through inhibition of 5-HT receptor activation by quinine, as we observed here. Furthermore, cells exhibited marked decreases in serotonin production during incubation with quinine. By assaying activity and kinetics of the rate-limiting enzyme for serotonin biosynthesis, tryptophan hydroxylase (TPH2), we showed that quinine competitively inhibits TPH2 in the presence of the substrate tryptophan. The study shows that quinine disrupts both serotonin biosynthesis and function, giving important new insight to the action of quinine on mammalian cells.

Item Type:	Article
Subjects:	QV Pharmacology > Autonomic Agents. Nonmetallic Elements. Neuromuscular Agents > QV 126 Neurotransmitters QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 256 Antimalarials QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 257 Cinchona and its derivatives QV Pharmacology > QV 38 Drug action. WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):	https://doi.org/10.1038/srep03618
Depositing User:	Lynn Roberts-Maloney
Date Deposited:	08 May 2015 10:19
Last Modified:	06 Feb 2018 13:09
URI:	https://archive.lstmed.ac.uk/id/eprint/5129

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