The antix2010amnesic and neuroprotective effects of donepezil against amyloid x03B22535 peptideinduced toxicity in mice involve an interaction with the x03C31 receptor - News Article - British Journal of Pharmacology The acetylcholinesterase inhibitor, donepezil, is also a high affinity ?1 receptor agonist. We examined the involvement of ?1 receptors in its anti-amnesic and neuroprotective properties against amyloid ?25-35 peptide-induced toxicity in mice. Mice were given an intracerebroventricular (i.c.v.) injection of A?25-35 peptide (9 nmol) 7-9 days before being tested for spontaneous alternation and passive avoidance. Hippocampal lipid peroxidation was measured 7 days after A?25-35 injection to evaluate oxidative stress. Donepezil, the ?1 agonist PRE-084 or the cholinesterase (ChE) inhibitors tacrine, rivastigmine and galantamine were administered either 20 min before behavioural sessions to check their anti-amnesic effects, or 20 min before A?25-35 injection, or 24 h after A?25-35 injection and then once daily before behavioural sessions, to check their pre- and post-i.c.v. neuroprotective activity, respectively. All the drugs tested were anti-amnesic, but only the effects of PRE-084 and donepezil were prevented by the ?1 antagonist BD1047. Only PRE-084 and donepezil showed neuroprotection when administered pre i.c.v.; they blocked lipid peroxidation and learning deficits, effects inhibited by BD1047. Post i.c.v., PRE-084 and donepezil showed complete neuroprotection whereas the other ChE inhibitors showed partial effects. BD1047 blocked these effects of PRE-084, attenuated those of donepezil, but did not affect the partial effects of the other ChE inhibitors. The potent anti-amnesic and neuroprotective effects of donepezil against A?25-35-induced toxicity involve both its cholinergic and ?1 agonistic properties. This dual action may explain its sustained activity compared to other ChE inhibitors. British Journal of Pharmacology (2006) 149, 998–1012.
DONEPEZIL TOXICITY
galantamine 16
