Effects of WEB 1881 FU, a Novel Nootropic, on Cholinergic and Adrenergic Receptors in the Rat Brain: Action on M₁-Muscarinic Receptors

Abstract

Effects of 4-aminomethyl-1-benzylpyrrolidin-2-one-hemifumarate (WEB 1881 FU), a novel pyrrolidinone nootropic, on acetylcholine (ACh) receptors and adrenoceptors were investigated using crude membranes of the rat brain. The affinity order of WEB 1881 FU was: M₁-muscarinic (m) ACh receptor>M₂-mACh receptor>α₂-adrenoceptor>β-adrenoceptor>α₁-adrenoceptor>nicotinic ACh receptor. The WEB 1881 FU-competition curve for [³H]pirenzepine binding in hippocampal membranes was rightward-shifted by GTPγS; such behavior was also observed in the case of oxotremorine but not with scopolamine. The effects of long-term administration of WEB 1881 FU (30 mg/kg/day, i.p.) for 21 days resulted in a significant decrease in the B_max of [³H]quinuclidinyl benzilate binding in the cerebral cortex, hippocampus and striatum. In addition, the B_max of [³H]pirenzepine binding to hippocampal and striatal membranes and that of [³H]AF-DX 116 binding to cerebellar membranes were significantly decreased as well. From these results, WEB 1881 FU seems to act on M₁-mACh receptors, and its long-term administration probably induces the down-regulation of mACh receptors, mainly M₁-mACh receptors in the hippocampus and striatum and M₂-mACh receptors in the cerebellum.