Post-ischemic administration of bifemelane hydrochloride prohibits ischemia-induced depletion of the muscarinic M1-receptor and its mRNA in the gerbil hippocampus.
Parallel determinations of muscarinic cholinergic M1 receptor (M1-R) binding and of M1-R mRNA levels were carried out in the gerbil hippocampus 14 days after 5 min of transient ischemia. Both were reduced in the ischemic tissue to about 50% of the levels found in sham-operated controls, indicating that the late loss of M1-R is probably dependent on decreased synthesis. Three administrations of bifemelane hydrochloride (15 mg/kg, i.p., just after ischemia and 6 and 12 h later) completely prevented neuronal death in the hippocampus and ischemia-induced losses of hippocampal M1-R and its mRNA. Since vascular dementia may depend upon the ischemia-induced losses in cholinergic communication in the hippocampus, these findings suggest that it may be possible to prevent its occurrence by post-ischemic treatment with bifemelane hydrochloride.
Ogawa
N
N
Department of Neuroscience, Okayama University Medical School, Japan.
Asanuma
M
M
Mizukawa
K
K
Hirata
H
H
Chou
H
H
Mori
A
A
D000818:Animals; D001559:Benzhydryl Compounds / Q000008:administration & dosage*; D015152:Blotting, Northern; D005849:Gerbillinae; D006624:Hippocampus / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D015151:Immunoblotting; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
D001559:Benzhydryl Compounds; D012333:RNA, Messenger; D011976:Receptors, Muscarinic; C031906:bifemelane