Muscarinic Receptor 1 Agonist Activity Of Novel Arecoline Derivatives In Alzheimer�s Dementia Models | 6046
ISSN: 2155-9872

Journal of Analytical & Bioanalytical Techniques
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Muscarinic Receptor 1 Agonist Activity of Novel Arecoline Derivatives in Alzheimer�s Dementia Models

International Conference & Exihibition On Analytical and Bioanalytical Techniques - 2010

Kanchugarakoppal S. Rangappa

ScientificTracks Abstracts: J Anal Bioanal Techniques

DOI: 10.4172/2155-9872.1000001

The cholinergic deficit in Alzheimer�s disease (AD) patient�s brain has intensified research efforts to test cholinomimetic approaches for efficacy in AD therapy. Various therapies may be of potential clinical use in AD. Among these are cholinergic agents including 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, we have synthesized five and six membered heterocyclic ring system attached arecoline basic nucleus ( N- methyl tetrahydropyridines) at 3 rd position. Subsequently the synthesized arecolines derivatives were subjected to in vitro muscarinic receptor 1 binding affinity studies using male wistar rat brain synaptosomal membrane (cerebral cortex) and also cell line culture studies and extended this in vitro studies to in vivo pharmacological evaluation of memory and learning in male wistar rats (Rodent memory evaluation, plus and Y maze studies). Some of our synthesized molecules have shown very potent M1 receptor agonist activity and significantly elevated the basal IP3 levels in vitro and also have decreased beta-amyloid (Abeta 40 and Abeta 42 ) deposition in cell lines culture. These molecules have also shown very good antidementia activity in rat dementia model. Conclusions: Molecules with electron donating group as a substitute, has shown very good affinity towards the M1 receptor in vitro and has also elicited beneficial effects in vivo memory and learning models.