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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 greater than M2-mACh receptor greater than alpha 2-adrenoceptor greater than beta-adrenoceptor greater than alpha 1-adrenoceptor greater than nicotinic ACh receptor. The WEB 1881 FU-competition curve for [3H]pirenzepine binding in hippocampal membranes was rightward-shifted by GTP gamma S; 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 Bmax of [3H]quinuclidinyl benzilate binding in the cerebral cortex, hippocampus and striatum. In addition, the Bmax 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.

Effects of WEB 1881 FU, a novel nootropic, on cholinergic and adrenergic receptors in the rat brain: Action on M1-muscarinic receptors.