{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:36:31Z","timestamp":1761006991508,"version":"build-2065373602"},"reference-count":29,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2016,5,2]],"date-time":"2016-05-02T00:00:00Z","timestamp":1462147200000},"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":[[2016,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The D1\/D2 dopamine agonist apomorphine has poor oral bioavailability, necessitating subcutaneous administration in the treatment of Parkinson's disease (PD). Acute subcutaneous injection is used as rescue therapy from \u201coff\u201d periods, whereas continuous subcutaneous infusion is used to increase \u201con\u201d periods and to reduce dyskinesia when oral treatment fails. An orally active derivative of apomorphine would avoid the need for parenteral administration. We now describe the effects of the orally active compound R\u2010(\u2010)\u201011\u2010O\u2010valeryl\u2010N\u2010<jats:italic>n<\/jats:italic>\u2010propylnoraporphine (11\u2010OH\u2010NPa valerate) on reversal of motor disability and expression of dyskinesia in 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine (MPTP)\u2010treated, <jats:sc>l<\/jats:sc>\u2010dopa\u2010primed dyskinetic common marmosets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Locomotor activity, motor disability, and dyskinesia were assessed in MPTP\u2010treated marmosets following the administration of apomorphine (0.075 mg\/kg, subcutaneous and 0.28 to 1.12 mg\/kg, oral) and 11\u2010OH\u2010NPa valerate (0.19, 0.38, and 0.75mg\/kg, oral).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Subcutaneous administration of apomorphine (0.075 mg\/kg) produced a short\u2010lasting reversal of motor disability and the expression of established dyskinesia, but when administered orally (0.28\u20101.12 mg\/kg) it had no effect. In contrast, oral treatment with 11\u2010OH\u2010NPa valerate (0.19 and 0.75 mg\/kg) induced a dose\u2010related reversal of motor disability and increased locomotor activity with only mild to moderate dyskinesia. Only at the highest dose (0.75 mg\/kg) was marked dyskinesia seen accompanying an extended period of motor disability reversal and increased locomotor activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Oral administration of 11\u2010OH\u2010NPa valerate produced a rapid reversal of motor disability and, at effective dose levels, had a limited propensity to induce dyskinesia. 11\u2010OH\u2010NPa valerate is the first orally active derivative of apomorphine with potential for use in PD. \u00a9 2016 International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.26626","type":"journal-article","created":{"date-parts":[[2016,5,2]],"date-time":"2016-05-02T01:05:26Z","timestamp":1462151126000},"page":"1381-1388","source":"Crossref","is-referenced-by-count":7,"title":["Oral r\u2010(\u2010)\u201011\u2010o\u2010valeryl\u2010n\u2010<i>n<\/i>\u2010propylnoraporphine reverses motor deficits in mptp\u2010treated marmosets"],"prefix":"10.1002","volume":"31","author":[{"given":"Louise","family":"Lincoln","sequence":"first","affiliation":[{"name":"Neurodegenerative Diseases Research Group, Faculty of Life Science and Medicine, Hodgkin Building, King's College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ria","family":"Fisher","sequence":"additional","affiliation":[{"name":"Neurodegenerative Diseases Research Group, Faculty of Life Science and Medicine, Hodgkin Building, King's College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Neurodegenerative Diseases Research Group, Faculty of Life Science and Medicine, Hodgkin Building, King's College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Jenner","sequence":"additional","affiliation":[{"name":"Neurodegenerative Diseases Research Group, Faculty of 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