Preventive effects of bifemelane hydrochloride on decreased levels of muscarinic acetylcholine receptor and its mRNA in a rat model of chronic cerebral hypoperfusion.
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.
Kondo
Y
Y
Department of Neuroscience, Institute of Molecular and Cellular Medicine, Okayama University Medical School, Okayama, Japan.
Ogawa
N
N
Asanuma
M
M
Matsuura
K
K
Nishibayashi
K
K
Iwata
E
E
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000188:drug therapy / Q000378:metabolism; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D015152:Blotting, Northern; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D002908:Chronic Disease; D004195:Disease Models, Animal; D005625:Frontal Lobe / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D018727:Muscarinic Antagonists / Q000378:metabolism / Q000494:pharmacology; D017072:Neostriatum / Q000187:drug effects; D018697:Nootropic Agents / Q000494:pharmacology*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000235:genetics*; D014316:Tritium
D001559:Benzhydryl Compounds; D018727:Muscarinic Antagonists; D018697:Nootropic Agents; D012333:RNA, Messenger; D011976:Receptors, Muscarinic; D014316:Tritium; D011813:Quinuclidinyl Benzilate; C031906:bifemelane