POSTISCHEMIC ADMINISTRATION OF BIFEMELANE HYDROCHLORIDE PROHIBITS ISCHEMIA-INDUCED DEPLETION OF THE MUSCARINIC M(1)-RECEPTOR AND ITS MESSENGER-RNA 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.