Effects of bifemelane hydrochloride on various cholinergic markers in cortical and subcortical regions of aged rats.

The effects of bifemelane hydrochloride (BF) upon various cholinergic markers, muscarinic receptors, acetylcholinesterase (AChE) and choline acetyltransferase (CAT), in the aged rat brain were examined. Marked reduction of the density of muscarinic receptors (Bmax) as well as AChE and CAT activity concomitant with aging was observed. Administration of BF in daily doses of 10 mg/kg for 4 weeks to aged rats significantly decreased the apparent dissociation constant (Kd) for QNB in muscarinic receptors in the forebrain, but did not affect the value of Bmax. CAT activity also increased significantly compared with that of control aged rats, but administration of BF did not alter AChE activity. These results indicate that long-term treatment with BF enhances the affinity of muscarinic receptors for QNB as well as CAT activity and that BF may have therapeutic application in the treatment of CNS cholinergic dysfunctions.