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In a blinded, placebo-controlled, randomized first-in-human study, JNJ-37822681 was administered orally to 27 healthy male volunteers at doses of 0.5, 2, 5, 10, 15 and 20\u2009mg. Safety, pharmacokinetics and central nervous system effects were evaluated by measuring prolactin levels, eye movements, adaptive tracking, visual analogue scales, body sway, finger tapping and electroencephalography. JNJ-37822681 was well tolerated and somnolence was the most frequently reported adverse effect. Peak plasma concentrations increased more than proportional to dose, but increases in the area under curve (AUC) were dose-proportional. Prolactin elevations started at doses of 5\u2009mg, whereas small decreases in adaptive tracking were demonstrated at 10\u2009mg doses. At higher doses, JNJ-37822681 caused a small decrease in saccadic peak velocity, smooth pursuit, alertness, finger tapping and electroencephalography activity, and an increase in body sway. This effect profile is likely to be the result of the selectivity of JNJ-37822681 for the D\n                    <jats:sub>2<\/jats:sub>\n                    receptor, leading to strong D\n                    <jats:sub>2<\/jats:sub>\n                    receptor-mediated elevations in serum prolactin, but fewer effects on more complex central nervous system functions, which are likely to involve multiple neurotransmitters.\n                  <\/jats:p>","DOI":"10.1177\/0269881111415733","type":"journal-article","created":{"date-parts":[[2011,9,3]],"date-time":"2011-09-03T20:13:21Z","timestamp":1315080801000},"page":"1119-1127","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["Pharmacokinetics and central nervous system effects of the novel dopamine D\n                    <sub>2<\/sub>\n                    receptor antagonist JNJ-37822681"],"prefix":"10.1177","volume":"26","author":[{"given":"Erik 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