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

Neurosci Res. 1996 Mar;24(4):409-14. doi: 10.1016/0168-0102(95)01017-3.

Abstract

Changes in muscarinic acetylcholine receptor (mACh-R) binding and muscarinic cholinergic m1 receptor (m1-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 percent, P <0.01), striatum (74.2 percent, P < 0.01) and hippocampus (78.6 percent, P < 0.01), and the m1-R mRNA levels in the frontal cortex (86.6 percent, P < 0.05) and striatum (89.4 percent, 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 m1-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arterial Occlusive Diseases / drug therapy
  • Arterial Occlusive Diseases / metabolism
  • Benzhydryl Compounds / pharmacology*
  • Blotting, Northern
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / metabolism
  • Chronic Disease
  • Disease Models, Animal
  • Frontal Lobe / drug effects
  • Gene Expression / drug effects
  • Hippocampus / drug effects
  • Male
  • Muscarinic Antagonists / metabolism
  • Muscarinic Antagonists / pharmacology
  • Neostriatum / drug effects
  • Nootropic Agents / pharmacology*
  • Quinuclidinyl Benzilate / metabolism
  • Quinuclidinyl Benzilate / pharmacology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Muscarinic / genetics*
  • Tritium

Substances

  • Benzhydryl Compounds
  • Muscarinic Antagonists
  • Nootropic Agents
  • RNA, Messenger
  • Receptors, Muscarinic
  • Tritium
  • Quinuclidinyl Benzilate
  • bifemelane