Administration of haloperidol with biperiden reduces mRNAs related to the ubiquitin-proteasome system in mice.
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.
Iwata
Shin-Ichi
S
Department of Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Kagoshima, Japan. shinichi@m.kufm.kagoshima-u.ac.jp
Morioka
Hirofumi
H
Iwabuchi
Mika
M
Shinohara
Kazuya
K
Maeda
Maki
M
Shimizu
Takao
T
Miyata
Atsuro
A
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*
D018492:Dopamine Antagonists; D004338:Drug Combinations; D018727:Muscarinic Antagonists; D012333:RNA, Messenger; D025801:Ubiquitin; D001712:Biperiden; D046988:Proteasome Endopeptidase Complex; D006220:Haloperidol