title: Effect of novel arecoline thiazolidinones as muscarinic receptor 1 agonist in Alzheimer's dementia models.
abstract: The discovery of cholinergic deficit in Alzheimer's disease (AD) patient's brain has triggered research efforts, using cholinomimetic approaches for their efficacy in AD therapy. Various therapies may be of potential clinical use in AD. Among these are cholinergic agents, which include muscarinic agonists, acetylcholinesterase inhibitors, and acetylcholine releasing agents. One of the muscarinic agonists tested in AD is arecoline and its bioisosters, which are widely explored as muscarinic receptor 1 agonist (M1 receptor agonist) in AD research. In this regard, five-membered heterocyclic ring system attached arecoline basic nucleus (N-methyl tetrahydropyridines) at third position has been extensively researched on. The present research involved synthesis of arecoline thiazolidinones 5(a-j) by using dipolar addition of 3-aminopyridine and alkyl/aryl carboxaldehydes in presence of gamma ferrite as catalyst. The resulting products were methylated and reduced to get desired products. Subsequently the synthesized arecoline thiazolidinones were subjected to in vitro muscarinic receptor binding studies using male Wistar rat brain (cerebral cortex) membrane homogenate and extended this in vitro study to in vivo pharmacological evaluation of memory and learning in male Wistar rats. Four derivatives (5a-5c and 5e) showed considerable M1 receptor binding affinity (in vitro) and elicited beneficial effects in vivo memory and learning models (Rodent memory evaluation, plus and Y maze studies).
authors: Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570006, India.
authors: J N Narendra Sharath
authors: JN
authors: Chandra
authors: Manish
authors: M
authors: Malviya
authors: C T
authors: CT
authors: Sadashiva
authors: M N
authors: MN
authors: Subhash
authors: Kanchugarakoppal S
authors: KS
authors: Rangappa
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001115:Arecoline / Q000031:analogs & derivatives / Q000138:chemical synthesis; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D015394:Molecular Structure; D018721:Muscarinic Agonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D043643:Receptor, Muscarinic M1 / Q000819:agonists* / Q000378:metabolism; D053778:Thiazolidines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology
chemical_list: D018721:Muscarinic Agonists; D043643:Receptor, Muscarinic M1; D053778:Thiazolidines; D001115:Arecoline; D000109:Acetylcholine