{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T10:47:29Z","timestamp":1772189249133,"version":"3.50.1"},"reference-count":61,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,2,11]],"date-time":"2014-02-11T00:00:00Z","timestamp":1392076800000},"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":[[2014,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Levodopa\u2010induced dyskinesias (LIDs) are a serious complication of levodopa therapy for Parkinson's disease for which there is little treatment. Accumulating evidence shows that nicotinic acetylcholine receptor (nAChR) drugs decrease LIDs in parkinsonian animals. Here, we examined the effect of two \u03b22 nAChR agonists, ABT\u2010089 and ABT\u2010894, that previously were approved for phase 2 clinical trials for other indications. Two sets of 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine (MPTP)\u2010lesioned monkeys were administered levodopa\/carbidopa (10 mg\/kg and 2.5 mg\/kg, respectively) twice daily 5 days a week until they were stably dyskinetic. Each set had a vehicle\u2010treated group, an nAChR agonist\u2010treated group, and a nicotine\u2010treated group as a positive control. Set A monkeys had previously received other nAChR drugs (nAChR drug\u2010primed), whereas Set B monkeys were initially nAChR drug\u2010naive. Both sets were administered the partial agonist ABT\u2010089 (range, 0.01\u20101.0 mg\/kg) orally 5 days a week twice daily 30 minutes before levodopa with each dose given for 1 to 5 weeks. ABT\u2010089 decreased LIDs by 30% to 50% compared with vehicle\u2010treated monkeys. Nicotine reduced LIDs by 70% in a parallel group. After 4 weeks of washout, the effect of the full agonist ABT\u2010894 (range, 0.0001\u20100.10 mg\/kg) was assessed on LIDs in Set A and Set B. ABT\u2010894 reduced LIDs by 70%, similar to nicotine. Both drugs acted equally well at \u03b14\u03b22* and \u03b16\u03b22* nAChRs; however, ABT\u2010089 was 30 to 60 times less potent than ABT\u2010894. Tolerance did not develop for the time periods tested (range, 3\u20104 months). The nAChR drugs did not worsen parkinsonism or cognitive ability. Emesis, a common problem with nAChR drugs, was not observed. ABT\u2010894 and ABT\u2010089 appear to be good candidate nAChR drugs for the management of LIDs in Parkinson's disease. \u00a9 2014 International Parkinson and Movement Disorder Society<\/jats:p>","DOI":"10.1002\/mds.25817","type":"journal-article","created":{"date-parts":[[2014,2,12]],"date-time":"2014-02-12T05:35:59Z","timestamp":1392183359000},"page":"508-517","source":"Crossref","is-referenced-by-count":40,"title":["ABT\u2010089 and ABT\u2010894 reduce levodopa\u2010induced dyskinesias in a monkey model of Parkinson's disease"],"prefix":"10.1002","volume":"29","author":[{"given":"Danhui","family":"Zhang","sequence":"first","affiliation":[{"name":"Center for Health Sciences SRI International Menlo Park California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanuja","family":"Bordia","sequence":"additional","affiliation":[{"name":"Center for Health Sciences SRI International Menlo Park California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"McGregor","sequence":"additional","affiliation":[{"name":"Center for Health Sciences SRI International Menlo Park California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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