Tacrine, a reversible acetylcholinesterase inhibitor, induces myopathy

Tacrine, an acetylcholinesterase (AChE) inhibitor that has been used in the treatment of Alzheimer's disease, increases available acetylcholine (Ach) levels in the synaptic cleft thereby enhancing the activity of cholinergic pathways. However, excessive stimulation of nicotinic receptors at the neuromuscular junction results in muscle deterioration. We tested whether reversible AChE inhibitors such as tacrine may induce similar effects. In the present study, tacrine administration (7.5 mg/kg twice daily) to rats produces a 20 and 30-fold increase in the number of degenerating cells in leg and diaphragm muscle, respectively, as compared to control. This myopathy is significantly decreased by co-administration of tacrine with the nitric oxide (NO) synthase inhibitor L-NAME. These results show that tacrine can induce myopathy which may be mediated by increased NO production.