Correspondence  |   July 2016
In Reply
Author Notes
  • Huashan Hospital, Fudan University, Shanghai, China.
  • (Accepted for publication March 30, 2016.)
    (Accepted for publication March 30, 2016.)×
Article Information
Correspondence   |   July 2016
In Reply
Anesthesiology 7 2016, Vol.125, 254-255. doi:
Anesthesiology 7 2016, Vol.125, 254-255. doi:
More and more evidence indicates that mefloquine potentially causes long-term mental health problems.1  And the U.S. Food and Drug Administration has recently added a boxed warning to mefloquine, advising of the possibility of neurologic and psychiatric adverse events even after drug withdrawal. We are quite sympathetic to Dr. Nevin’s proposals of considerations in the repositioning of mefloquine for an anesthetic. However, we have our own opinion about considering mefloquine, or its ameliorated form, as a potential analgesic candidate in the future.
It is undeniable that mefloquine has a forceful effect as an antimalarial.2  For this reason, mefloquine could obtain the new drug license from the Food and Drug Administration in 1989 and was listed on the World Health Organization’s List of Essential Medicines as well. Moreover, in our previous work, we found that the development of neuropathic pain could be retarded evidently by systematic administration of mefloquine.3  Although it was a small sample research, the effect of mefloquine was very precise.
Since mefloquine is confirmed as a selective connexin (Cx) 36 blocker,4,5  we chose it as a tool for verifying the contribution of Cx36 in the pathologic process of neuropathic pain. And we therefore suggested that Cx36 could be a new target for pain management. We certainly realized the possibility of neurologic and psychiatric adverse effects of mefloquine. In our study, we sought to find out the active isomer of mefloquine [(−)-(11R, 12S)-mefloquine] for further investigation. Our future effort is to try developing a new analgesic with more specificity for the target site and substantially reduced toxicity by molecular modification. That work is bound to need multilateral cooperation with plenty of time, before the new drug is officially certified.
Last, we would like to emphasize that our work is just in the stage of animal investigation. We totally agree with Dr. Nevin’s words, that is, any attempt for off-label prescribing of the drug for analgesia would clearly be unethical without precautions. There should be more laboratory studies until expansion of clinical researches.
Research Support
The work was supported by a grant from the National Natural Science Funds of China, Beijing, China (grant no. 81171169).
Competing Interests
The author declares no competing interests.
Ying-Wei Wang, M.D., Ph.D., Huashan Hospital, Fudan University, Shanghai, China.
Nevin, RL Idiosyncratic quinoline central nervous system toxicity: Historical insights into the chronic neurological sequelae of mefloquine.. Int J Parasitol Drugs Drug Resist. (2014). 4 118–25 [Article] [PubMed]
Schlagenhauf, P, Adamcova, M, Regep, L, Schaerer, MT, Rhein, HG The position of mefloquine as a 21st century malaria chemoprophylaxis.. Malar J. (2010). 9 357 [Article] [PubMed]
Chen, ZY, Shen, FY, Jiang, L, Zhao, X, Shen, XL, Zhong, W, Liu, S, Wang, ZR, Wang, YW Attenuation of neuropathic pain by inhibiting electrical synapses in the anterior cingulate cortex.. Anesthesiology. (2016). 124 169–83 [Article] [PubMed]
Bissiere, S, Zelikowsky, M, Ponnusamy, R, Jacobs, NS, Blair, HT, Fanselow, MS Electrical synapses control hippocampal contributions to fear learning and memory.. Science. (2011). 331 87–91 [Article] [PubMed]
Cruikshank, SJ, Hopperstad, M, Younger, M, Connors, BW, Spray, DC, Srinivas, M Potent block of Cx36 and Cx50 gap junction channels by mefloquine.. Proc Natl Acad Sci U S A. (2004). 101 12364–9 [Article] [PubMed]