{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T15:54:37Z","timestamp":1761580477552},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2007,2,23]],"date-time":"2007-02-23T00:00:00Z","timestamp":1172188800000},"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":[[2007,6]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>To present a case of piloerection after replacing fluvoxamine maleate with milnacipran hydrochloride, and to analyse this effect based on receptor occupancy theory.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A 40\u2010year\u2010old female with a 3\u2010year history of panic disorder was prescribed fluvoxamine 50\u2003mg\u2003day<jats:sup>\u22121<\/jats:sup> in addition to clorazepate dipotassium and sulpiride. Depression was not improved and she complained of fatigue, lack of energy and drowsiness. These symptoms worsened within a few days of an increase in the dose of fluvoxamine to 50\u2003mg twice daily. Since an interaction between fluvoxamine and tizanidine, prescribed by another clinic, was suspected, fluvoxamine was replaced with milnacipran 50\u2003mg day<jats:sup>\u22121<\/jats:sup>. Although her drowsiness improved, she complained of piloerection throughout her body. This symptom gradually abated within a week and when the dosage of milnacipran was increased to 100\u2003mg day<jats:sup>\u22121<\/jats:sup> at 2 months, no further piloerection occurred. We calculated the changes in \u03b1<jats:sub>1<\/jats:sub>\u2010adrenoceptor occupancy by endogenous norepinephrine during treatment with the usual doses of milnacipran, fluvoxamine and imipramine by using pharmacokinetic and pharmacodynamic parameters obtained from the literature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The ratios of \u03b1<jats:sub>1<\/jats:sub>\u2010adrenoceptor occupancy by endogenous norepinephrine during the treatment with milnacipran, fluvoxamine and imipramine to that without drug were estimated to be 7.13, 1.00 and 4.12, respectively. The \u03b1<jats:sub>1<\/jats:sub>\u2010adrenoceptor occupancy by endogenous norepinephrine was increased in a dose\u2010dependent manner by milnacipran, whereas fluvoxamine had essentially no effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The piloerection observed after the replacement of fluvoxamine with milnacipran in this patient appears to have been due to an increase in the \u03b1<jats:sub>1<\/jats:sub>\u2010adrenoceptor occupancy by endogenous norepinephrine induced by milnacipran.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2125.2006.02838.x","type":"journal-article","created":{"date-parts":[[2007,2,24]],"date-time":"2007-02-24T04:16:38Z","timestamp":1172290598000},"page":"665-671","source":"Crossref","is-referenced-by-count":5,"title":["Piloerection induced by replacing fluvoxamine with 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