Peripheral cholinoceptor antagonist anisodamine counteracts cholinergic adverse effects and facilitates cognitive amelioration of rivastigmine
| Autor: | Wei-Wei Zhang, Juan Li, Yong-Yao Cui, Zheng Xia, Ming-Ke Song, Biyun Shao, Hong-Zhuan Chen, Hao Wang, Zu-Peng Xu |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Scopolamine Phenylcarbamates Mice Inbred Strains Rivastigmine Pharmacology Solanaceous Alkaloids Cholinergic Antagonists Anisodamine chemistry.chemical_compound Mice Random Allocation Cognition medicine Avoidance Learning Animals Adverse effect Biological Psychiatry Cognitive deficit Cholinesterase Muscle Cramp biology Antagonist Peripheral Nervous System Diseases Intestines Psychiatry and Mental health Neuroprotective Agents Neurology Tolerability chemistry biology.protein Cholinergic Drug Therapy Combination Neurology (clinical) medicine.symptom Psychology Cognition Disorders Salivation medicine.drug |
| Zdroj: | Journal of neural transmission (Vienna, Austria : 1996). 116(12) |
| ISSN: | 1435-1463 |
| Popis: | Rivastigmine is a potent acetyl- and butyrylcholinesterase inhibitor widely used for cognitive improvement in Alzheimer’s disease (AD) therapy. However, dose-limiting adverse effects restrict its tolerability and clinical outcomes. This study explored new combined therapy, in which peripheral cholinergic adverse effects and central cognitive amelioration of rivastigmine were differentiated by a peripheral cholinoceptor antagonist anisodamine. The results demonstrated that rivastigmine (0.75 and 2.0 mg/kg) could significantly reverse the scopolamine-induced cognitive deficit in mice through passive avoidance test. Nevertheless, a high dose of rivastigmine (3.25 mg/kg) would compromise cognitive amelioration and produce obvious adverse effects, including hypersalivation, intestinal hyperperistalsis and muscle cramp. Interestingly, concomitant administration of anisodamine (10 mg/kg) effectively counteracted both the muscarinergic and nicotinergic adverse effects, while facilitating cognitive amelioration of rivastigmine (3.25 mg/kg). These findings provide an insight into the feasibility of combined therapy with cholinesterase inhibitors and peripheral cholinoceptor antagonists for the treatment of AD. |
| Databáze: | OpenAIRE |
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