Prolonged Administration of Pyridostigmine Impairs Neuromuscular Function with and without Down-regulation of Acetylcholine Receptors

Abstract

Prolonged administration of pyridostigmine (25 mg·kg·day) leads to neuromuscular impairment, which can persist even when pyridostigmine is discontinued 24 h before assessment of neuromuscular function. Pyridostigmine has the potential to down-regulate acetylcholine receptors, but induces neuromuscular dysfunction even in the absence of receptor changes.

Induction of distinct neuroinflammatory markers and gut dysbiosis by differential pyridostigmine bromide dosing in a chronic mouse model of GWI showing persistent exercise fatigue and cognitive impairment

“…Downregulation of muscarinic AChRs after prolonged exposure to another AChEI, sarin, has also been shown [ 72 ]. Reduced cholinergic signaling can also be produced by desensitization and inactivation of AChRs after prolonged AChE inhibition [ 73 , 74 ]. Receptor desensitization due to prolonged activation of muscarinic receptors has been implicated as the root cause for inhibition of hippocampal LTP induction [ 75 ], the cellular manifestation of associative learning [ 76 ].…”

Persistent exercise fatigue and associative learning deficits in combination with transient glucose dyshomeostasis in a mouse model of Gulf War Illness

“…For example, reduced muscle and/or subcortical levels of ATP have been found in GWI mice [87]. Alternatively, morphological data from PB-treated mice showing structural changes in skeletal muscle [88] may explain, in part, intolerance to exercise in GW2. Central mechanisms may also contribute to exercise fatigue such as increased tryptophan-kynurenic acid pathway activity within the hypothalamus-hippocampal circuit and disturbances in the serotonergic system implicated in different fatigue models [89,90].…”

Cholinergic Stimulation by Pyridostigmine Bromide Before Myocardial Infarction Prevent Cardiac and Autonomic Dysfunction

“…However, evidence in the literature suggests that prolonged exposure to high-dose PYR (i.e., 28 days) may cause essential side-effects on the neuromuscular apparatus, including reduced tetanic tension 38 . Additionally, a recent study-case described the presence of leukocytoclastic vasculitis in a 91-year-old man who was treated for two weeks with PYR 39 .…”