Article: Mefloquine

Mefloquine
Systematic (IUPAC) name
2,8-bis(trifluoromethyl)quinolin-4-yl]-(2-piperidyl)methanol
Identifiers
CAS number	53230-10-7
ATC code	P01BC02
PubChem	4046
DrugBank	APRD00300
Chemical data
Formula	C17H16F6N2O
Mol. weight	378.312 g/mol
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half life	2 to 4 weeks
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status
Routes	oral

Mefloquine is an orally administered antimalarial drug used as a prophylaxis against and treatment for malaria. It also goes by the trade name Lariam® (manufactured by Roche Pharmaceuticals) and chemical name mefloquine hydrochloride (forumulated with HCl). Mefloquine was developed in the 1970s at the Walter Reed Army Institute of Research in the U.S. as a chemical synthetic similar to quinine.

Uses

Mefloquine is used to prevent malaria (malaria prophylaxis) and also in the treatment of chloroquine-resistant falciparum malaria. As mefloquine resistance spreads, mefloquine has started to lose its efficacy.

Mefloquine is the drug of choice in chloroquine-resistant Plasmodium vivax.^[1]

Advice to travelers

Mefloquine is one of the antimalarial drugs which the August 2005 issue of the CDC Travel Health Yellow Sheet advises travelers in areas with malaria risk — Africa, South America, the Indian subcontinent, Asia, and the South Pacific — to take.

There are virulent strains of malaria that are resistant to one or more anti-malarial drugs; for example, there are mefloquine-resistant strains in Thailand, Cambodia and Myanmar. Travelers are advised to compare current recommendations before selecting an antimalarial drug as the occurrence of drug-resistant strains changes.

The CDC, the UK Guidelines for Malaria Prevention, and the WHO provide up-to-date recommendations for specific countries.

The drug is taken once a week starting at least one week prior to entry into malaria endemic areas and continued for 4 weeks after leaving. Owing to the risk of neuropsychiatric disturbance, particularly disruption of sleep, UK advice is for people who have not previously used Mefloquine to start 3 weeks prior to departure; adverse effects usually manifest within one or two weeks, and so there would remain sufficient time to switch to an alternative drug.

Side-effects

Like many other drugs, mefloquine has adverse side-effects. It is known to cause severe depression, anxiety, paranoia, nightmares, insomnia, vestibular (balance) damage and central nervous system problems. For a complete list of adverse physical and psychological effects — including suicidal ideation — see the most recent product information. In 2002 the word "suicide" was added to the official product label, though proof of causation has not been established. Since 2003, the Food and Drug Administration (FDA) has required that patients be screened before mefloquine is prescribed. Anyone taking antidepressants or with a history of psychiatric illness should not take mefloquine. The latest Consumer Medication Guide to Lariam has more complete information.

In the 1990s there were reports in the media [1]that the drug may have played a role in the Somalia Affair, which involved the torture and murder of a Somali citizen whilst in the custody of Canadian peacekeeping troops. There has been similar controversy since three murder-suicides involving Special Forces soldiers at Fort Bragg, N.C., in the summer of 2002. To date more than 19 cases of vestibular damage following the use of mefloquine have been diagnosed by military physicians. The same damage has been diagnosed among business travelers and tourists.

Neurological activity

In 2004, researchers found that mefloquine in adult mice blocks connexins called Cx36 and Cx50. Cx36 is found in the brain and Cx50 is located in the eye lens. Connexins in the brain are believed to play a role in movement, vision and memory.

Chirality and its implications

Mefloquine is a chiral molecule. It contains two asymmetric carbons, which means there are a total of four different enantiomers of the molecule. Mefloquine is currently manufactured and sold as a racemate of the (+/-) R*,S* enantiomers by Hoffman-LaRoche, a Swiss pharmaceutical company. According to some research, the (+) enantiomer is more effective in treating malaria, and the (-) enantiomer specifically binds to adenosine receptors in the central nervous system, which may explain some of its psychotropic effects. Some believe that it is irresponsible for a pharmaceutical company to sell mefloquine as a racemic mixture. It is not known whether mefloquine goes through stereoisomeric switching in vivo.