Effects of (±)-huprine Y and (±)-huprine Z, two new anticholinesterasic drugs, on muscarinic receptors

Abstract

The cholinergic profile of (±)-huprine Y and (±)-huprine Z on muscarinic receptors has been determined. Displacement of [ 3H]-pirenzepine and [ 3H]-QNB plus pirenzepine was performed in rat hippocampus. Both compounds showed a higher degree of affinity to M 1 muscarinic receptors ( P < 0.01) than to M 2 muscarinic receptors. To determine the M 1 agonist or antagonist role of the two huprines, studies of inositol phosphates (IP) production were performed. Both huprines significantly stimulated IP accumulation in a concentration-dependent manner. The reversion of this effect by different antagonists showed that M 1 muscarinic receptors were activated by (±)-huprine Y and (±)-huprine Z, but some other mechanisms, such as α 1-adrenoceptors or nicotinic receptors, were involved.