Logo Medical Science Monitor Basic Research

Call: 1.631.470.9640
Mon-Fri 10 am - 2 pm EST

Contact Us

Logo Medical Science Monitor Basic Research Logo Medical Science Monitor Basic Research Logo Medical Science Monitor Basic Research

15 July 2013 : Hypothesis  

Mefloquine use, psychosis, and violence: A retinoid toxicity hypothesis

Anthony MawsonEF

DOI: 10.12659/MSM.889033

Med Sci Monit 2013; 19:579-583

Abstract

ABSTRACT: Mefloquine use has been linked to severe gastrointestinal and neuropsychiatric adverse effects, including cognitive disturbances, anxiety, depression, psychosis, and violence. The adverse effects of the drug are thought to result from the secondary consequences of hepatocellular injury; in fact, mefloquine is known to cause a transient, anicteric chemical hepatitis. However, the mechanism of mefloquine-associated liver damage and the associated neuropsychiatric and behavioral effects of the drug are not well understood. Mefloquine and other 8-amino-quinolines are the only antimalarial drugs that target the liver-stage malaria parasites, which selectively absorb vitamin A from the host. Vitamin A is also stored mainly in the liver, in potentially poisonous concentrations. These observations suggest that both the therapeutic effectiveness of mefloquine and its adverse effects are related to the ability of the 8-aminoquinolines to alter the metabolism of retinoids (vitamin A and its congeners). Several lines of evidence support the hypothesis that mefloquine neurotoxicity and other adverse effects reflect an endogenous form of hypervitaminosis A due to a process involving: mefloquine-induced dehydrogenase inhibition; the accumulation of retinoids in the liver; retinoid-induced hepatocellular damage; the spillage of stored retinoids into the circulation; and the transport of these compounds to the gut and brain in toxic concentrations. The retinoid hypothesis could be tested clinically by comparing cases of mefloquine toxicity and untreated controls in terms of retinoid profiles (retinol, retinyl esters, percent retinyl esters, and retinoic acid). Subject to such tests, retinoid profiling could provide an indicator for assessing mefloquine-associated adverse effects.

Keywords: Drug-Induced Liver Injury - metabolism, Aggression - drug effects, Hypervitaminosis A - etiology, Liver - metabolism, Malaria - drug therapy, Mefloquine - therapeutic use, Models, Biological, Oxidoreductases - antagonists & inhibitors, Psychoses, Substance-Induced - etiology, Retinoids - metabolism

0 Comments

Most Viewed Current Articles

13 Apr 2020 : Original article  

Outcome of 24 Weeks of Combined Schroth and Pilates Exercises on Cobb Angle, Angle of Trunk Rotation, Chest...

DOI :10.12659/MSMBR.920449

Med Sci Monit Basic Res 2020; 26:e920449

11 May 2020 : Original article  

Analysis of Psychological and Sleep Status and Exercise Rehabilitation of Front-Line Clinical Staff in the ...

DOI :10.12659/MSMBR.924085

Med Sci Monit Basic Res 2020; 26:e924085

05 Jan 2021 : Review article  

A Southeast Asian Perspective on the COVID-19 Pandemic: Hemoglobin E (HbE)-Trait Confers Resistance Against...

DOI :10.12659/MSMBR.929207

Med Sci Monit Basic Res 2021; 27:e929207

10 Aug 2020 : Clinical Research  

Effects of Cognitive Task Training on Dynamic Balance and Gait of Patients with Stroke: A Preliminary Rando...

DOI :10.12659/MSMBR.925264

Med Sci Monit Basic Res 2020; 26:e925264

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor Basic Research eISSN: 2325-4416
Medical Science Monitor Basic Research eISSN: 2325-4416