Abstract：
AIMS:In a previous study it was demonstrated that the anxiolytic action of tandospirone, a 5-hydroxytryptamine (5-HT)(1A) receptor agonist, is facilitated by cytochrome P450 (CYP) 3A4 inhibitors, such as ketoconazole and cimetidine. It is also known that fluvoxamine, a selective serotonin re-uptake inhibitor (SSRI), inhibits CYP3A4. The purpose of the present study was to clarify the pharmacokinetic interaction between tandospirone and fluvoxamine and to evaluate their combined effect in the rat anxiety model. METHODS:The anxiolytic action of co-administration of tandospirone and fluvoxamine was examined using the rat contextual conditioned fear stress model. After testing the conditioned fear, plasma concentrations of tandospirone and its major metabolite 1-(2-pyrimidyl) piperazine were determined. RESULTS:One day after fear conditioning, both tandospirone (60 mg/kg, p.o.) and fluvoxamine (60 mg/kg, p.o.) significantly inhibited conditioned freezing and their combination effect was additive. In addition, plasma concentration of tandospirone was increased by fluvoxamine. CONCLUSIONS:There is a CYP3A4-related drug-drug interaction between tandospirone and fluvoxamine. Therefore, fluvoxamine may facilitate the anxiolytic effect of tandospirone via CYP3A4 inhibition.
journal_name
Psychiatry Clin Neuroscijournal_title
Psychiatry and clinical neurosciencesauthors
Nishikawa H,Inoue T,Masui T,Izumi T,Nakagawa S,Koyama Tdoi
10.1111/j.1440-1819.2008.01853.xsubject
Has Abstractpub_date
2008-10-01 00:00:00pages
591-6issue
5eissn
1323-1316issn
1440-1819pii
PCN1853journal_volume
62pub_type
杂志文章abstract：:In September 1987 in Japan, the Mental Hygiene Law was amended to the Mental Health Law. This Law emphasizes the protection of human rights of the mentally disabled as well as the promotion of their social rehabilitation. In 1993, Mental Health Law was partially revised in the following four areas: (i) social rehabili...
journal_title：Psychiatry and clinical neurosciences
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journal_title：Psychiatry and clinical neurosciences
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