{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T14:23:04Z","timestamp":1792678984446,"version":"4.5.0"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,3,17]],"date-time":"2017-03-17T00:00:00Z","timestamp":1489708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Centrally\u2010acting acutely anxiolytic drugs, such as benzodiazepines, barbiturates and gabapentinoids, affect various central nervous system (CNS) functions, which reflects not only their anxiolytic effects but also neuropsychological side\u2010effects. To validate the pharmacodynamic biomarkers for GABA\u2010ergic anxiolytics, this study determined the pharmacodynamics of two anxiolytics and a nonanxiolytic control, and linked them to their anxiolytic and sedative effects, during an anxiety\u2010challenge study day.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty healthy volunteers were randomized in this placebo\u2010controlled, double\u2010blind, four\u2010way cross\u2010over study with single\u2010dose alprazolam (1\u00a0mg), diphenhydramine (50\u00a0mg), pregabalin (200\u00a0mg) or placebo. The Neurocart was used between repeated fear\u2010potentiated startle assessments. Thus, the potential influence of anxiety on CNS pharmacodynamic markers could be examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to placebo, VAS<jats:sub>calmness<\/jats:sub> increased with alprazolam (2.0\u00a0mm) and pregabalin (2.5\u00a0mm) but not with diphenhydramine. Saccadic peak velocity (SPV) declined after alprazolam (\u221257\u00a0\u00b0\u00a0s<jats:sup>\u20131<\/jats:sup>) and pregabalin (\u221228\u00a0\u00b0\u00a0s<jats:sup>\u20131<\/jats:sup>), more than with diphenhydramine (\u221214\u00a0\u00b0\u00a0s<jats:sup>\u20131<\/jats:sup>); so did smooth pursuit. The average responses of SPV and smooth pursuit were significantly correlated with the drug\u2010induced increases in VAS<jats:sub>calmness<\/jats:sub>. The SPV\u2010relative responses of VAS<jats:sub>alertness<\/jats:sub>, body\u2010sway and adaptive\u2010tracking also differed among alprazolam, pregabalin and diphenhydramine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Compared with the antihistaminergic sedative diphenhydramine, alprazolam and pregabalin caused larger SPV reduction, which was correlated with simultaneous improvement of subjective calmness, during a study day in which anxiety was stimulated repeatedly. The different effect profiles of the three drugs are in line with their pharmacological distinctions. These findings corroborate the profiling of CNS effects to demonstrate pharmacological selectivity, and further support SPV as biomarker for anxiolysis involving GABA\u2010ergic neurons. The study also supports the use of prolonged mild threat to demonstrate anxiolytic effects in healthy volunteers.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13204","type":"journal-article","created":{"date-parts":[[2016,12,6]],"date-time":"2016-12-06T10:28:47Z","timestamp":1481020127000},"page":"1028-1038","source":"Crossref","is-referenced-by-count":28,"title":["Pharmacodynamic response profiles of anxiolytic and sedative drugs"],"prefix":"10.1111","volume":"83","author":[{"given":"Xia","family":"Chen","sequence":"first","affiliation":[{"name":"Phase I Unit, Clinical Pharmacology Research Center Peking Union Medical College Hospital  Beijing 100032 China"},{"name":"Centre for Human Drug Research  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Freerk","family":"Broeyer","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research  Leiden The 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