s
i
ANANBIOANAL - 2010
Pharmaceutical R & D Summit
doi:10.4172/2155-9872.1000016
Muscarinic Receptor 1 Agonist Activity of Novel Arecoline
Derivatives in Alzheimer’s Dementia Models
Kanchugarakoppal S. Rangappa
DOS in Chemistry, Manasagangotri, University of Mysore, Mysore, India
T
he 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 3rd
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 (Abeta40
Abeta42
and
) 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.
ANALBIOANAL-2010
O
M
I
C
S
P
i
u
h
b
l
n
g
G
r
o
u
p