TY - JOUR
T1 - Review of the mechanism underlying mefloquine-induced neurotoxicity
AU - Martins, Airton C.
AU - Paoliello, Monica M.B.
AU - Docea, Anca O.
AU - Santamaria, Abel
AU - Tinkov, Alexey A.
AU - Skalny, Anatoly V.
AU - Aschner, Michael
N1 - Publisher Copyright:
© 2021 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2021
Y1 - 2021
N2 - Mefloquine, a potent blood schizontocide, is effective against drug-resistant Plasmodium falciparum. This property, along with its unique pharmacokinetic profile, makes mefloquine a widely prescribed antimalarial drug. However, several epidemiological studies have raised concerns on the safety of mefloquine as prophylaxis for malaria. Well-documented side-effects of mefloquine include abnormal dreams, insomnia, anxiety, and depressed mood, as well as nausea and dizziness (the last two most frequent effects). The mechanisms that underlie the neurological/psychiatric complications of mefloquine are poorly understood. The aim of this study was to review the literature on the neurotoxic mechanisms of action of mefloquine to better understand its potential toxicity in the central nervous system, highlighting the mechanisms that lead to its psychiatric disorders. Experimental studies on the neurotoxic effects of mefloquine discussed herein include brain transporters of mefloquine, alteration in neurotransmitters, disruption on calcium (Ca2+) homeostasis and neuroinflammation, generation of oxidative stress response in neurons (involving glutathione, increased F2-isoprostanes, accumulation of cytosolic lipid globules), and alteration of voltage-dependent channels, as well as gap junction intercellular communications. Although several hypotheses have been proposed for the mechanisms that mediate mefloquine-induced brain damage, they are not fully understood, necessitating additional studies in the future.
AB - Mefloquine, a potent blood schizontocide, is effective against drug-resistant Plasmodium falciparum. This property, along with its unique pharmacokinetic profile, makes mefloquine a widely prescribed antimalarial drug. However, several epidemiological studies have raised concerns on the safety of mefloquine as prophylaxis for malaria. Well-documented side-effects of mefloquine include abnormal dreams, insomnia, anxiety, and depressed mood, as well as nausea and dizziness (the last two most frequent effects). The mechanisms that underlie the neurological/psychiatric complications of mefloquine are poorly understood. The aim of this study was to review the literature on the neurotoxic mechanisms of action of mefloquine to better understand its potential toxicity in the central nervous system, highlighting the mechanisms that lead to its psychiatric disorders. Experimental studies on the neurotoxic effects of mefloquine discussed herein include brain transporters of mefloquine, alteration in neurotransmitters, disruption on calcium (Ca2+) homeostasis and neuroinflammation, generation of oxidative stress response in neurons (involving glutathione, increased F2-isoprostanes, accumulation of cytosolic lipid globules), and alteration of voltage-dependent channels, as well as gap junction intercellular communications. Although several hypotheses have been proposed for the mechanisms that mediate mefloquine-induced brain damage, they are not fully understood, necessitating additional studies in the future.
KW - Mefloquine
KW - Pyk2
KW - calcium homeostasis
KW - neurotoxicity
KW - oxidative stress
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U2 - 10.1080/10408444.2021.1901258
DO - 10.1080/10408444.2021.1901258
M3 - Review article
C2 - 33905310
AN - SCOPUS:85105178527
SN - 1040-8444
VL - 51
SP - 209
EP - 216
JO - Critical reviews in toxicology
JF - Critical reviews in toxicology
IS - 3
ER -