Preventive effects of bifemelane hydrochloride on decreased levels of muscarinic acetylcholine receptor and its mRNA in a rat model of chronic cerebral hypoperfusion

Yoichi Kondo, Norio Ogawa, Masato Asanuma, Koji Matsuura, Sakiko Nishibayashi, Emi Iwata

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Changes in muscarinic acetylcholine receptor (mACh-R) binding and muscarinic cholinergic ml receptor (ml-R) mRNA levels were determined in a rat model of cerebral hypoperfusion in which hypoperfusion was induced by permanent bilateral occlusion of the common carotid arteries. After 6 weeks of hypoperfusion, mACh-R binding activity was significantly reduced in the frontal cortex (79.0%, P <0.01), striatum (74.2%, P <0.01) and hippocampus (78.6%, P <0.01), and the ml-R mRNA levels in the frontal cortex (86.6%, P <0.05) and striatum (89.4%, P <0.05) compared with sham-operated control. Repeated administration of bifemelane hydrochloride (15 mg/kg/day, p.o., once a day from the day of operation for 6 weeks) prevented the hypoperfusion-induced loss of mACh-R binding and ml-R mRNA levels above described. Since the central cholinergic systems play an important role in learning and memory, these findings suggest that bifemelane hydrochloride is useful to treat and/or prevent vascular dementia which is closely related to cerebral hypoperfusion.

Original languageEnglish
Pages (from-to)409-414
Number of pages6
JournalNeuroscience Research
Issue number4
Publication statusPublished - Mar 1996



  • 2VO
  • Bifemelane hydrochloride
  • Cholinergic system
  • Chronic cerebral hypoperfusion
  • Permanent occlusion
  • Vascular dementia

ASJC Scopus subject areas

  • Neuroscience(all)

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