Differentiating effects of anisodamine on cognitive amelioration and peripheral muscarinic side effects induced by pilocarpine in mice.

Based on the cholinergic hypothesis of Alzheimer's disease (AD), many cholinomimetics have been tested for the treatment of AD. Although some of them have beneficial effects, peripheral muscarinic side effects limit their utility. Our present experiments showed that muscarinic agonist pilocarpine (pilo) could significantly improve memory deficits induced by scopolamine in step-through task, but be accompanied by pronounced peripheral cholinergic side effects such as hypersalivation, bradycardia, diarrhea and so on. Anisodamine (aniso) is a peripheral muscarinic blocker isolated from a Chinese herb Anisodus tanguticus and is widely used in China. When combined with aniso, pilo preserved its central efficacy with very minor peripheral side effects. Cholinomimetics combined with peripheral muscarinic blockers may provide alternative therapeutic strategies for AD.