Effects of Bifemelane on Muscarinic Receptors and Choline Acetyltransferase in the Brains of Aged Rats Following Chronic Cerebral Hypoperfusion Induced by Permanent Occlusion of Bilateral Carotid Arteries

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Cerebral hypoperfusion was chronically induced in aged rats via permanent bilateral occlusion of common carotid arteries (2VO). Marked reduction of the B<SUB>max</SUB> value of the muscarinic receptors (mAChR) in both the cortex and striatum and the V<SUB>max</SUB> value of choline acetyltransferase (ChAT) activity in the cortex, hippocampus and striatum were observed as compared with those of control aged rats. No significant changes in mAChR and ChAT activity were observed between young control rats and young 2VO rats. One month post-surgery in aged rats, daily doses of bifemelane (10 mg/kg) or aniracetam (50 mg/kg) were administered orally over a 4-week period. Administration of bifemelane significantly increased B<SUB>max</SUB> values and decreased apparent K<SUB>d</SUB> Values for <SUP>3</SUP>H-quinuclidinyl benzilate (QNB) in mAChR in the striatum. Chronic administration of bifemelane or aniracetam also enhanced ChAT activity in the cortex, hippocampus and striatum. In particular, administration of bifemelane resulted in a significant increase in V<SUB>max</SUB> values of ChAT in all three brain regions, while no significant change in K<SUB>m</SUB> values for ChAT was observed. These results suggest that bifemelane is responsible for this activity, thereby enhancing the functioning system of CNS cholinergic neurons of cerebral hypoperfused aged rats.


  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 72(1), 57-65, 1996-09-01

    The Japanese Pharmacological Society

References:  32

Cited by:  5


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