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.

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