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 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.