{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T10:59:39Z","timestamp":1758970779513,"version":"3.38.0"},"reference-count":56,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2011,5,12]],"date-time":"2011-05-12T00:00:00Z","timestamp":1305158400000},"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":[[2011,6]]},"abstract":"<jats:p><jats:bold>WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT<\/jats:bold><\/jats:p><jats:p>\u2022\u2003Several lines of evidence suggest a possible role of 5\u2010HT<jats:sub>6<\/jats:sub>receptor antagonists in dementia or cognitive dysfunction of schizophrenia. SB\u2010742457 is a potent 5\u2010HT<jats:sub>6<\/jats:sub>antagonist and has shown efficacy in different animal models of cognitive impairment. It is currently in development as a cognitive enhancer. Risperidone, commonly used to control agitation and psychotic features in both schizophrenia and Alzheimer's disease, is a D<jats:sub>2<\/jats:sub>\/5\u2010HT<jats:sub>2A<\/jats:sub>antagonist with low affinity for 5\u2010HT<jats:sub>6<\/jats:sub>receptors and limited effects on cognitive parameters.<\/jats:p><jats:p><jats:bold>WHAT THIS STUDY ADDS<\/jats:bold><\/jats:p><jats:p>\u2022\u2003As the combination of risperidone and SB\u2010742457 may constitute a reasonable combination in cognitively impaired patients, pharmacodynamic interaction effects were investigated in this study. The only significant drug\u2013drug interaction was a small increase of electroencephalogram (EEG) alpha and beta bands, which might suggest mild arousing activity of SB\u2010742457 on the central nervous system\u2010depressant effects of risperidone. The clinical relevance of these findings in patients remains to be established. Additionally, this study provided an extensive multidimensional pharmacodynamic profile of risperidone in healthy volunteers, showing that this antipsychotic suppresses motor performance (eye\u2013hand coordination, finger tapping and postural stability), alertness, memory and neurophysiological functions (saccadic eye movements and EEG power spectrum).<\/jats:p><jats:p><jats:bold>AIM<\/jats:bold>Several lines of evidence suggest a possible role of 5\u2010HT<jats:sub>6<\/jats:sub>receptor antagonists in cognitive dysfunction of schizophrenia. Atypical antipsychotics, such as risperidone, are currently used in these disorders. Therefore, the pharmacological interactions between the 5\u2010HT<jats:sub>6<\/jats:sub>antagonist SB\u2010742457 and risperidone were investigated in the light of possible co\u2010medication.<\/jats:p><jats:p><jats:bold>METHODS<\/jats:bold>A randomized, double\u2010blind, two\u2010way crossover design was used to study the interaction between multiple doses SB\u2010742457 50\u2003mg and a single dose risperidone 2\u2003mg in 18 healthy subjects.<\/jats:p><jats:p><jats:bold>RESULTS<\/jats:bold>Treatment was well tolerated. The most common adverse event was somnolence in 83% during the combination<jats:italic>vs.<\/jats:italic>50% of subjects after risperidone, 32% after placebo and 11% after SB\u2010742457. Combination treatment produced a statistically significant increase in the maximum plasma concentration of risperidone and had no effect on SB\u2010742457 pharmacokinetics. Risperidone decreased saccadic peak velocity, finger tapping, adaptive tracking, subjective alertness, delayed word recognition and body sway and increased electroencephalogram (EEG) theta power and prolactin. The only pharmacodynamic interaction of risperidone and SB\u2010742457 was an increase of absolute EEG alpha (ratio = 1.25, 95% CI = 1.11, 1.40,<jats:italic>P<\/jats:italic>= 0.0004) and beta power (ratio = 1.14, 95% CI = 1.03, 1.27,<jats:italic>P<\/jats:italic>= 0.016). No significant effects of SB\u2010742457 alone were found.<\/jats:p><jats:p><jats:bold>CONCLUSION<\/jats:bold>The pharmacokinetic interactions between SB\u2010742457 and risperidone detected in this study were not clinically relevant. The increase in EEG alpha and beta power is incompatible with enhanced risperidone activity, but could point to mild arousing effects of the combination. Most pharmacodynamic changes of risperidone are consistent with previously reported data. The potential cognitive effects of SB\u2010742457 remain to be established.<\/jats:p>","DOI":"10.1111\/j.1365-2125.2011.03902.x","type":"journal-article","created":{"date-parts":[[2011,1,11]],"date-time":"2011-01-11T18:35:34Z","timestamp":1294770934000},"page":"907-916","source":"Crossref","is-referenced-by-count":19,"title":["Central nervous system effects of the interaction between risperidone (single dose) and the 5\u2010HT<sub>6<\/sub>antagonist SB742457 (repeated doses) in healthy men"],"prefix":"10.1111","volume":"71","author":[{"given":"Marieke","family":"Liem\u2010Moolenaar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mandana","family":"Rad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Zamuner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam F.","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Lemme","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kari L.","family":"Franson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joop M. 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