title: Administration of haloperidol with biperiden reduces mRNAs related to the ubiquitin-proteasome system in mice.
abstract: In order to find molecules affected by administration of an antipsychotic drug with an antimuscarinic drug, which is a common prescription used to prevent extrapyramidal adverse effects caused by the antipsychotic drugs, gene expression profiling in the frontal cortex was studied in mice. After 14 days of administration with 2 mg/kg haloperidol, a typical antipsychotic drug, and 2 mg/kg biperiden, a high-affinity antagonist for muscarinic receptors in the brain, approximately 500 mRNAs related to synaptic function were investigated. The levels of the mRNAs related to the ubiquitin-related systems were significantly reduced after the combined administration. However, the separate administration of either haloperidol or biperiden had little effect on the levels of the mRNAs. This result suggests that coadministration of haloperidol and biperiden specifically affects the ubiquitin-related system.
authors.affiliation: Department of Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Kagoshima, Japan. shinichi@m.kufm.kagoshima-u.ac.jp
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Iwata
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Morioka
authors.forename: Mika
authors.initials: M
authors.lastname: Iwabuchi
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shinohara
authors.forename: Maki
authors.initials: M
authors.lastname: Maeda
authors.forename: Takao
authors.initials: T
authors.lastname: Shimizu
authors.forename: Atsuro
authors.initials: A
authors.lastname: Miyata
mesh_terms: D000818:Animals; D001712:Biperiden / Q000008:administration & dosage*; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects*; D004338:Drug Combinations; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D006220:Haloperidol / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*
chemical_list: D018492:Dopamine Antagonists; D004338:Drug Combinations; D018727:Muscarinic Antagonists; D012333:RNA, Messenger; D025801:Ubiquitin; D001712:Biperiden; D046988:Proteasome Endopeptidase Complex; D006220:Haloperidol