title: Tacrine, a reversible acetylcholinesterase inhibitor, induces myopathy.
abstract: 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.
authors.affiliation: The Parkinson's Institute, Sunnyvale, CA 94089, USA.
authors.forename: G
authors.initials: G
authors.lastname: Jeyarasasingam
authors.forename: M
authors.initials: M
authors.lastname: Yeluashvili
authors.forename: M
authors.initials: M
authors.lastname: Quik
mesh_terms: D000818:Animals; D002800:Cholinesterase Inhibitors / Q000009:adverse effects*; D003964:Diaphragm / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D009135:Muscular Diseases / Q000139:chemically induced* / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013619:Tacrine / Q000009:adverse effects* / Q000037:antagonists & inhibitors
chemical_list: D002800:Cholinesterase Inhibitors; D004791:Enzyme Inhibitors; D013619:Tacrine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester