title: Mefloquine blockade of Pannexin1 currents: resolution of a conflict.
abstract: The authors' laboratory has reported potent block of Pannexin1 (Panx1) currents by the antimalarial quinine derivative mefloquine. However, other laboratories have found little or no mefloquine sensitivity of Panx1 currents or processes attributable to these channels. In order to resolve this issue, the authors have performed extensive dose-response studies on Panx1-transfected neuroblastoma (Neuro2A) and rat insulinoma (Rin) cells, comparing mefloquine obtained from three suppliers and also comparing the sensitivity to diastereomers. Results indicate a 20-fold difference in sensitivity to the (-)-threo-(11R/2R) diastereomer compared to the erythro enatiomers and much lower potency of (+/-)-erythro-(R*/S*)-mefloquine obtained from one of the commercial sources. This markedly lower efficacy presumably accounts for the disparity in results from different laboratories who have applied it in Panx1 studies.
authors.affiliation: Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Iglesias
authors.forename: David C
authors.initials: DC
authors.lastname: Spray
authors.forename: Eliana
authors.initials: E
authors.lastname: Scemes
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015640:Ion Channel Gating / Q000187:drug effects*; D015767:Mefloquine / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D000962:Antimalarials; D017630:Connexins; D009419:Nerve Tissue Proteins; C503631:Panx1 protein, mouse; D011993:Recombinant Fusion Proteins; D015767:Mefloquine