Interaction of a new potent anticholinesterasic compound (+/-)huprine X with muscarinic receptors in rat brain.

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 [(3)H]pirenzepine or [(3)H]quinuclinidylbenzylate to hippocampus preparations was inhibited by (+/-)huprine X. This drug displayed a greater affinity for M(1) (K(i)=0.338+/-0.41 microM) than M(2) (K(i)=4.66+/-0.32 microM) receptors. In functional studies, (+/-)huprine X (1 microM) increased the release of [(3)H]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 microM) on [(3)H]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.