Interaction of a new potent anticholinesterasic compound (±)huprine X with muscarinic receptors in rat brain

Abstract

The interaction of rac-12-amine-3-clor-6,7,10,11-tetrahydro-9-ethyl-7-11-methanecyclo-octane[ b]quinoline ((±)huprine X) with M 1 and M 2 receptors has been studied in rat brain. Specific binding of [ 3H]pirenzepine or [ 3H]quinuclinidylbenzylate to hippocampus preparations was inhibited by (±)huprine X. This drug displayed a greater affinity for M 1 ( K i =0.338±0.41 μM) than M 2 ( K i =4.66±0.32 μM) receptors. In functional studies, (±)huprine X (1 μM) increased the release of [ 3H]dopamine in cortical synaptosomes, and this effect was partially reverted by atropine and mecamylamine, suggesting an agonistic effect on both M 1 and nicotinic receptors. The inhibitory effect of (±)huprine X (10 μM) on [ 3H]acetylcholine release and the subsequent reversion by atropine suggests that the drug also has an agonist effect on M 2 receptors. The present results demonstrate that this acetylcholinesterase inhibitor has an ample cholinergic profile, which suggests a potential source of interest of (±)huprine X in Alzheimer's disease therapy.