Journal
PSYCHOPHARMACOLOGY
Volume 231, Issue 14, Pages 2771-2783Publisher
SPRINGER
DOI: 10.1007/s00213-014-3446-0
Keywords
Mefloquine; Chloroquine; Quinine; Malaria; LSD; Psychotomimetic; Neurotransmitter; Transporter; Serotonin receptor; Dopamine receptor
Categories
Funding
- National Institute on Drug Abuse [1P50 DA018165]
- NIH/VA Interagency Agreement [ADA 12013]
- V.A. Merit Review [1I01BX000939-01]
- V.A. Research Career Scientist Program
- Bill and Melinda Gates Foundation
Ask authors/readers for more resources
Mefloquine is used for the prevention and treatment of chloroquine-resistant malaria, but its use is associated with nightmares, hallucinations, and exacerbation of symptoms of post-traumatic stress disorder. We hypothesized that potential mechanisms of action for the adverse psychotropic effects of mefloquine resemble those of other known psychotomimetics. Using in vitro radioligand binding and functional assays, we examined the interaction of (+)- and (-)-mefloquine enantiomers, the non-psychotomimetic anti-malarial agent, chloroquine, and several hallucinogens and psychostimulants with recombinant human neurotransmitter receptors and transporters. Hallucinogens and mefloquine bound stereoselectively and with relatively high affinity (K (i) = 0.71-341 nM) to serotonin (5-HT) (2A) but not 5-HT1A or 5-HT2C receptors. Mefloquine but not chloroquine was a partial 5-HT2A agonist and a full 5-HT2C agonist, stimulating inositol phosphate accumulation, with similar potency and efficacy as the hallucinogen dimethyltryptamine (DMT). 5-HT receptor antagonists blocked mefloquine's effects. Mefloquine had low or no affinity for dopamine D-1, D-2, D-3, and D-4.4 receptors, or dopamine and norepinephrine transporters. However, mefloquine was a very low potency antagonist at the D-3 receptor and mefloquine but not chloroquine or hallucinogens blocked [H-3]5-HT uptake by the 5-HT transporter. Mefloquine, but not chloroquine, shares an in vitro receptor interaction profile with some hallucinogens and this neurochemistry may be relevant to the adverse neuropsychiatric effects associated with mefloquine use by a small percentage of patients. Additionally, evaluating interactions with this panel of receptors and transporters may be useful for characterizing effects of other psychotropic drugs and for avoiding psychotomimetic effects for new pharmacotherapies, including antimalarial quinolines.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available