{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T12:52:44Z","timestamp":1777467164166,"version":"3.51.4"},"reference-count":69,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2006,6,13]],"date-time":"2006-06-13T00:00:00Z","timestamp":1150156800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2006,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Excessive olivo\u2010cerebellar synchrony is implicated in essential tremor. Because synchrony in some networks is mediated by gap junctions, we examined whether the gap junction blockers heptanol, octanol, carbenoxolone, and mefloquine suppress tremor in the mouse harmaline model, and performed an open\u2010treatment clinical study of mefloquine for essential tremor. Digitized motion was used to quantify tremor in mice administered harmaline, 20 mg\/kg s.c. In mice the broad\u2010spectrum gap junction blockers heptanol, octanol (350 mg\/kg i.p. each), and carbenoxolone (20 mg\/kg) suppressed harmaline tremor. Mefloquine (50 mg\/kg), which blocks gap junctions containing connexin 36, robustly suppressed harmaline tremor. Glycyrrhizic acid (related to carbenoxolone) and chloroquine (related to mefloquine), which do not block gap junctions, failed to suppress harmaline tremor in mice. Clinically, tremor was assessed with standard rating scales, and subjects asked to take 62.5, 125, and 250 mg mefloquine weekly for 12 weeks at each dose. None of the four human subjects showed a meaningful tremor reduction with mefloquine, likely because clinical levels were below those required for efficacy. In view of recent genetic evidence, the anti\u2010tremor mechanism of these compounds is uncertain but may represent a novel therapeutic target, possibly involving gap junctions other than those containing connexin 36. \u00a9 2006 Movement Disorder Society<\/jats:p>","DOI":"10.1002\/mds.20940","type":"journal-article","created":{"date-parts":[[2006,6,13]],"date-time":"2006-06-13T13:07:15Z","timestamp":1150204035000},"page":"1641-1649","source":"Crossref","is-referenced-by-count":49,"title":["Carbenoxolone and mefloquine suppress tremor in the harmaline mouse model of essential tremor"],"prefix":"10.1002","volume":"21","author":[{"given":"Fredricka C.","family":"Martin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian","family":"Handforth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,6,13]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/124.11.2278"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.73.4.400"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awg132"},{"key":"e_1_2_6_5_2","first-page":"118","article-title":"Glucose hypermetabolism of the inferior olive in patients with essential tremor","volume":"22","author":"Dubinsky R","year":"1987","journal-title":"Ann Neurol"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410340115"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410360413"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410410108"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(02)00966-7"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.25.3.259"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410390515"},{"key":"e_1_2_6_12_2","doi-asserted-by":"crossref","first-page":"2825","DOI":"10.1523\/JNEUROSCI.17-08-02825.1997","article-title":"Differential roles of apamin\u2010 and charybdotoxin\u2010sensitive K+ conductances in the generation of inferior olive rhythmicity in vivo","volume":"17","author":"Lang EJ","year":"1997","journal-title":"J Neurosci"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3907-04.2004"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00477.2001"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00236557"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(73)90768-3"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00231139"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1986.sp016147"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(76)91016-7"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1248\/bpb1978.4.520"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(84)90329-1"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(86)90165-2"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.20331"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00353.2005"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.13.7573"},{"key":"e_1_2_6_26_2","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s002320001094","article-title":"Functional expression of the murine connexin 36 gene coding for a neuron\u2010specific gap junctional protein","volume":"176","author":"Teubner B","year":"2000","journal-title":"J Membrane Biol"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)02300-3"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0173(99)00068-5"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-24-10898.2002"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2002.tb07582.x"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-11-04700.2003"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0402044101"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002130050809"},{"key":"e_1_2_6_34_2","first-page":"271","volume-title":"Parkinson's Disease and Movement Disorders","author":"Fahn SE","year":"1993"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(93)90036-P"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002280050351"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.20147"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870110306"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.49.1.64"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.56.4.475"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.35.10.1494"},{"issue":"1","key":"e_1_2_6_42_2","doi-asserted-by":"crossref","first-page":"C195","DOI":"10.1152\/ajpcell.1990.258.2.C195","article-title":"Structure\u2010activity relations of the cardiac gap junction channel","volume":"258","author":"Spray DC","year":"1990","journal-title":"Am J Physiol"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/61.2.132"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2210-3-3"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2003.10.047"},{"key":"e_1_2_6_46_2","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1128\/AAC.41.3.677","article-title":"Antimalarial activity of the bisquinoline trans\u2010N1,N2\u2010bis (7\u2010chloroquinolin\u20104\u2010yl)cyclohexane\u20101,2\u2010diamine: comparison of two stereoisomers and detailed evaluation of the S,S enantiomer, Ro 47\u20107737","volume":"41","author":"Ridley RG","year":"1997","journal-title":"Antimicrob Agents Chemother"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.1051\/parasite\/200209151"},{"key":"e_1_2_6_48_2","first-page":"68","article-title":"Pharmacokinetics of prophylactic mefloquine in Thai healthy volunteers","volume":"22","author":"Karbwang J","year":"1991","journal-title":"Southeast Asian J Trop Med Public Health"},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00585623"},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.1159\/000238195"},{"key":"e_1_2_6_51_2","first-page":"219","article-title":"Quantitative comparison of toxicity of anticancer agents in mouse, rat, hamster, dog, monkey, and man","volume":"50","author":"Freireich EJ","year":"1966","journal-title":"Cancer Chemother Rep"},{"key":"e_1_2_6_52_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3156.1996.d01-85.x"},{"key":"e_1_2_6_53_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1708-8305.1999.tb00843.x"},{"key":"e_1_2_6_54_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400322101"},{"key":"e_1_2_6_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00373-7"},{"key":"e_1_2_6_56_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000095581.20961.7D"},{"key":"e_1_2_6_57_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1998.79.1.240"},{"key":"e_1_2_6_58_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb15413.x"},{"key":"e_1_2_6_59_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb16042.x"},{"key":"e_1_2_6_60_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.053439"},{"key":"e_1_2_6_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703638"},{"key":"e_1_2_6_62_2","volume-title":"Gap junction channel blockers are antagonists of the p2x7 receptor","author":"Scemes E","year":"2004"},{"key":"e_1_2_6_63_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1469-04.2004"},{"key":"e_1_2_6_64_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19981116)401:2<163::AID-CNE2>3.0.CO;2-D"},{"key":"e_1_2_6_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(03)00077-0"},{"key":"e_1_2_6_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbrainres.2004.09.026"},{"key":"e_1_2_6_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1627"},{"key":"e_1_2_6_68_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2233464100"},{"key":"e_1_2_6_69_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2005.04139.x"},{"key":"e_1_2_6_70_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02947.x"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmds.20940","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.20940","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T13:27:54Z","timestamp":1760966874000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.20940"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,6,13]]},"references-count":69,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2006,10]]}},"alternative-id":["10.1002\/mds.20940"],"URL":"https:\/\/doi.org\/10.1002\/mds.20940","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,6,13]]}}}