Complex membrane channel blockade

A unifying hypothesis for the prodromal and acute neuropsychiatric sequelae resulting from exposure to the antimalarial drug Mefloquine

Research output: Contribution to journalArticle

5 Citations (Scopus)
10 Downloads (Pure)

Abstract

The alkaloid toxin quinine and its derivative compounds have been used for many centuries as effective medications for the prevention and treatment of malaria. More recently, synthetic derivatives, such as the quinoline derivative mefloquine (bis(trifluoromethyl)-(2-piperidyl)-4-quinolinemethanol), have been widely used to combat disease caused by chloroquine-resistant strains of the malaria parasite, Plasmodium falciparum. However, the parent compound quinine, as well as its more recent counterparts, suffers from an incidence of adverse neuropsychiatric side effects ranging from mild mood disturbances and anxiety to hallucinations, seizures, and psychosis. This review considers how the pharmacology, cellular neurobiology, and membrane channel kinetics of mefloquine could lead to the significant and sometimes life-threatening neurotoxicity associated with mefloquine exposure. A key role for mefloquine blockade of ATP-sensitive potassium channels and connexins in the substantia nigra is considered as a unifying hypothesis for the pathogenesis of severe neuropsychiatric events after mefloquine exposure in humans.
Original languageEnglish
Article number368064
Pages (from-to)1-12
Number of pages12
JournalJournal of Parasitology Research
Volume2015
DOIs
Publication statusPublished - 2015

Fingerprint

Mefloquine
Antimalarials
Ion Channels
Quinine
KATP Channels
Connexins
Neurobiology
Falciparum Malaria
Hallucinations
Chloroquine
Substantia Nigra
Alkaloids
Psychotic Disorders
Malaria
Parasites
Seizures
Anxiety
Pharmacology
Incidence

Cite this

@article{15289ddf977240a09af532b7d2e76ebb,
title = "Complex membrane channel blockade: A unifying hypothesis for the prodromal and acute neuropsychiatric sequelae resulting from exposure to the antimalarial drug Mefloquine",
abstract = "The alkaloid toxin quinine and its derivative compounds have been used for many centuries as effective medications for the prevention and treatment of malaria. More recently, synthetic derivatives, such as the quinoline derivative mefloquine (bis(trifluoromethyl)-(2-piperidyl)-4-quinolinemethanol), have been widely used to combat disease caused by chloroquine-resistant strains of the malaria parasite, Plasmodium falciparum. However, the parent compound quinine, as well as its more recent counterparts, suffers from an incidence of adverse neuropsychiatric side effects ranging from mild mood disturbances and anxiety to hallucinations, seizures, and psychosis. This review considers how the pharmacology, cellular neurobiology, and membrane channel kinetics of mefloquine could lead to the significant and sometimes life-threatening neurotoxicity associated with mefloquine exposure. A key role for mefloquine blockade of ATP-sensitive potassium channels and connexins in the substantia nigra is considered as a unifying hypothesis for the pathogenesis of severe neuropsychiatric events after mefloquine exposure in humans.",
keywords = "Adenosine triphosphate sensitive potassium channel, Antidepressant agent, Antimalarial agent, Artesunate, Chloroquine, Dihydroartemisinin, Gap junction protein, Mefloquine, Potassium channel, Proguanil, Quinine derivative, Quinoline derivative",
author = "Jane Quinn",
note = "Includes bibliographical references.",
year = "2015",
doi = "10.1155/2015/368064",
language = "English",
volume = "2015",
pages = "1--12",
journal = "Journal of Parasitology Research",
issn = "2090-0023",
publisher = "Hindawi Publishing Corporation",

}

TY - JOUR

T1 - Complex membrane channel blockade

T2 - A unifying hypothesis for the prodromal and acute neuropsychiatric sequelae resulting from exposure to the antimalarial drug Mefloquine

AU - Quinn, Jane

N1 - Includes bibliographical references.

PY - 2015

Y1 - 2015

N2 - The alkaloid toxin quinine and its derivative compounds have been used for many centuries as effective medications for the prevention and treatment of malaria. More recently, synthetic derivatives, such as the quinoline derivative mefloquine (bis(trifluoromethyl)-(2-piperidyl)-4-quinolinemethanol), have been widely used to combat disease caused by chloroquine-resistant strains of the malaria parasite, Plasmodium falciparum. However, the parent compound quinine, as well as its more recent counterparts, suffers from an incidence of adverse neuropsychiatric side effects ranging from mild mood disturbances and anxiety to hallucinations, seizures, and psychosis. This review considers how the pharmacology, cellular neurobiology, and membrane channel kinetics of mefloquine could lead to the significant and sometimes life-threatening neurotoxicity associated with mefloquine exposure. A key role for mefloquine blockade of ATP-sensitive potassium channels and connexins in the substantia nigra is considered as a unifying hypothesis for the pathogenesis of severe neuropsychiatric events after mefloquine exposure in humans.

AB - The alkaloid toxin quinine and its derivative compounds have been used for many centuries as effective medications for the prevention and treatment of malaria. More recently, synthetic derivatives, such as the quinoline derivative mefloquine (bis(trifluoromethyl)-(2-piperidyl)-4-quinolinemethanol), have been widely used to combat disease caused by chloroquine-resistant strains of the malaria parasite, Plasmodium falciparum. However, the parent compound quinine, as well as its more recent counterparts, suffers from an incidence of adverse neuropsychiatric side effects ranging from mild mood disturbances and anxiety to hallucinations, seizures, and psychosis. This review considers how the pharmacology, cellular neurobiology, and membrane channel kinetics of mefloquine could lead to the significant and sometimes life-threatening neurotoxicity associated with mefloquine exposure. A key role for mefloquine blockade of ATP-sensitive potassium channels and connexins in the substantia nigra is considered as a unifying hypothesis for the pathogenesis of severe neuropsychiatric events after mefloquine exposure in humans.

KW - Adenosine triphosphate sensitive potassium channel

KW - Antidepressant agent

KW - Antimalarial agent

KW - Artesunate

KW - Chloroquine

KW - Dihydroartemisinin

KW - Gap junction protein

KW - Mefloquine

KW - Potassium channel

KW - Proguanil

KW - Quinine derivative

KW - Quinoline derivative

U2 - 10.1155/2015/368064

DO - 10.1155/2015/368064

M3 - Article

VL - 2015

SP - 1

EP - 12

JO - Journal of Parasitology Research

JF - Journal of Parasitology Research

SN - 2090-0023

M1 - 368064

ER -