Effects of WEB 1881 FU, a novel nootropic, on cholinergic and adrenergic receptors in the rat brain: action on M1-muscarinic receptors.
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.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Y
Y
Kitamura
S
S
Hayashi
Y
Y
Nomura
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D020120:Iodocyanopindolol; D007700:Kinetics; D008297:Male; D009538:Nicotine / Q000378:metabolism; D010276:Parasympatholytics / Q000494:pharmacology*; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects* / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013873:Thionucleotides / Q000494:pharmacology; D015016:Yohimbine / Q000378:metabolism
D010276:Parasympatholytics; D011760:Pyrrolidinones; D011941:Receptors, Adrenergic; D011976:Receptors, Muscarinic; D013873:Thionucleotides; D015016:Yohimbine; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D010890:Pirenzepine; D011813:Quinuclidinyl Benzilate; D009538:Nicotine; D020120:Iodocyanopindolol; D006160:Guanosine Triphosphate; D010869:Pindolol; C048593:otenzepad; C056640:nebracetam; D011224:Prazosin