Mefloquine inhibits cholinesterases at the mouse neuromuscular junction

  title={Mefloquine inhibits cholinesterases at the mouse neuromuscular junction},
  author={Joseph J. McArdle and Lawrence C. Sellin and Kathleen M. Coakley and Joseph G. Potian and Mary C. Quinones-Lopez and Clint A Rosenfeld and Lester G. Sultatos and Kormakur Hognason},

Mefloquine enhances nigral gamma-aminobutyric acid release via inhibition of cholinesterase.

Data suggest that mefloquine enhances GABA release through its inhibition of cholinesterase, which allows accumulation of endogenously released acetylcholine, which activates neuronal nicotinic receptors on GABAergic nerve terminals.

Mefloquine Enhances Nigral γ-Aminobutyric Acid Release via Inhibition of Cholinesterase

Data suggest that mefloquine enhances GABA release through its inhibition of cholinesterase, which allows accumulation of endogenously released acetylcholine, which activates neuronal nicotinic receptors on GABAergic nerve terminals.

Review of the mechanism underlying mefloquine-induced neurotoxicity

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.

Antagonistic postsynaptic and presynaptic actions of cyclohexanol on neuromuscular synaptic transmission and function

The results explain the pattern of neuromuscular dysfunction following ingestion of organophosphorus insecticides containing cyclo hexanol precursors and suggest that cyclohexanol may facilitate investigation of mechanisms regulating synaptic strength at NMJs.

Cellular targets of mefloquine.

Acetylcholine Release in Mouse Motor Synapses. Changes of Purinergic Regulation under Conditions of Pharmacological Blockade of Pannexin 1 and Its Genetic Knockout

It was concluded that the lack of expression of the pannexin 1 gene caused by its knockout and acute blockade of pan Nexin 1 equally affected the secretion of ACh due to a decrease in the concentration of purines in the synaptic cleft.

Adverse neuropsychiatric effects of antimalarial drugs

A more systematic approach to assess the neuropsychiatric adverse effects of new or repurposed antimalarial drugs on their safety, tolerability and efficacy phases of clinical studies and in post-marketing surveillance, is needed to ensure that these life-saving tools remain available and can be prescribed with appropriate caution and medical judgment.

Activity of mefloquine and mefloquine derivatives against Echinococcus multilocularis

Efficacy of THN201, a Combination of Donepezil and Mefloquine, to Reverse Neurocognitive Deficits in Alzheimer’s Disease

It was demonstrated that the Cx modulator mefloquine (MEF) significantly enhanced the procognitive effect of DPZ in both models and local genetic silencing of astrocyte Cxs in the hippocampus was found to enhance the proc cognitive effect ofDPZ, pointing out the importance of Cx-dependent astroCyte networks in memory processes.



Cerebral uptake of mefloquine enantiomers in fatal cerebral malaria.

Based on the ratios brain concentration/plasma concentration, the brain penetration of the (+) enantiomer is much higher than that of the (-)Enantiomer, and the mechanism underlying the neurotoxicity is unknown.

Butyrylcholinesterase and acetylcholinesterase activity and quantal transmitter release at normal and acetylcholinesterase knockout mouse neuromuscular junctions

The results suggest that inhibition or absence of AChE increases evoked quantal release by involving muscarinic receptors (mAChRs), while BChE inhibition decreases release through direct or indirect mechanisms not involving mAChRs.

The cholinesterases: from genes to proteins.

These recent events have added a new perspective to cholinesterase research wherein all facets of gene expression become amenable to study and structure-function relation­ ships within this family of enzymes can be approached at an atomic level.

Tetrahydroaminoacridine (tacrine) stimulates neurosecretion at mammalian motor endplates

The neurosecretion evoked by tacrine could explain the therapeutic effects of the drug claimed in the treatment of Alzheimer's type of dementia and supports the idea that proximo‐distal axonal transport is required for the secretory activity.

Reduced acetylcholine receptor density, morphological remodeling, and butyrylcholinesterase activity can sustain muscle function in acetylcholinesterase knockout mice

The ability of diaphragm muscles from AChE−/− mice to maintain tension at 70 and 100 Hz suggests a partial compensation for impairment of acetylcholine (ACh) hydrolysis, and three mechanisms—including a reliance on BChE activity for termination of ACh action, downregulation of nicotinic acetyl choline receptors (nAChRs), and morphological remodeling of the endplate region—were identified.

Site of fasciculin interaction with acetylcholinesterase.

In the case of the mutant cholinesterases where rates of fasciculin dissociation are more rapid, steady state kinetic parameters also show acetylthiocholine-fasciculin competition to be consistent with occupation at a peripheral or substrate inhibition site rather than the active center.

CNS Adverse Events Associated With Antimalarial Agents

CNS adverse drug events are dramatic, and case reports have influenced clinical opinion on the use of antimalarials, and data do not suggest a need to diminish the correct use of the quinoline and artemisinin derivatives.

4-Aminoquinoline-induced ‘giant’ miniature endplate potentials at mammalian neuromuscular junctions

  • J. MolgóS. Thesleff
  • Biology, Medicine
    Proceedings of the Royal Society of London. Series B. Biological Sciences
  • 1982
Electrophysiological findings and a statistical analysis of the characteristicsofthe m.

Interactions of rat brain acetylcholinesterase with the detergent Triton X-100 and the organophosphate paraoxon.

Results suggest that measurement of acetylcholinesterase activity in the presence of up to 1% Triton X-100, but in the absence of oxon, should pose no problems with regard to data interpretation, provided it is recognized that the detergent slightly elevates activity.