Disease relevance of pyridostigmine

• A 59-year-old woman with myasthenia gravis who received a large dose of pyridostigmine bromide developed postoperative psychosis and was diagnosed as having bromide intoxication [1].
• Pyridostigmine bromide and constipation in Parkinson's disease [2].
• The GH responses to arginine (30 g i.v. over 30 min), L-dopa (0.5 g orally), insulin hypoglycemia (0.1 U/Kg i.v.), clonidine (0.25 mg orally), or pyridostigmine (60 mg orally) were measured in healthy young men after pretreatment with either saline of GHRH-Ant 400 microgram/kg i.v. In every case, GH release was significantly suppressed by GHRH-Ant [3].
• Heterozygous carriers of the deletion included a proband who presented with acute hypersensitivity to the anti-AChE pyridostigmine and another with unexplained excessive vomiting during a fourth pregnancy following three spontaneous abortions [4].
• Pyridostigmine for fibromyalgia: comment on the article by Paiva and a historical vignette [5].

Psychiatry related information on pyridostigmine

• Consideration of this phenomenon becomes urgent in view of the large-scale prophylactic use of the anti-ChE, pyridostigmine, during the 1991 Persian Gulf War, in anticipation of nerve gas attack and of the anti-ChE, tacrine, for improving residual cholinergic neurotransmission in Alzheimer's disease patients [6].
• Elevated growth hormone responses to pyridostigmine in obsessive-compulsive disorder: evidence of cholinergic supersensitivity [7].
• Arginine but not pyridostigmine, a cholinesterase inhibitor, enhances the GHRH-induced GH rise in patients with anorexia nervosa [8].
• An increased pyridostigmine/GH response is also found in affective disorders and could be related to nonspecific symptoms common to all these diagnostic groups [9].
• Enhanced growth hormone responses to pyridostigmine challenge in patients with panic disorder [10].

High impact information on pyridostigmine

• Here we report that after mice were subjected to a forced swim protocol (shown previously to simulate stress), an increase in blood-brain barrier permeability reduced the pyridostigmine dose required to inhibit mouse brain AChE activity by 50% to less than 1/100th of the usual dose [11].
• Unexpectedly, under a similar regimen, pyridostigmine administration during the Persian Gulf War resulted in a greater than threefold increase in the frequency of reported central nervous system symptoms [11].
• Under these conditions, peripherally administered pyridostigmine increased the brain levels of c-fos oncogene and AChE mRNAs [11].
• CONCLUSION: Three new findings are reported: 1) FM patients have a reduced GH response to exercise, 2) pyridostigmine reverses this impaired response, and 3) defective GH secretion in FM can occur in patients with normal IGF-1 levels [12].
• Effect of pyridostigmine bromide on serum bromide concentration and the anion gap [13].

Chemical compound and disease context of pyridostigmine

• Effect of growth hormone (GH)-releasing hormone (GHRH), atropine, pyridostigmine, or hypoglycemia on GHRP-6-induced GH secretion in man [14].
• Treatment of Lambert-Eaton syndrome: 3,4-diaminopyridine and pyridostigmine [15].
• This review deals mainly with the pharmacokinetics of the reversible quaternary cholinesterase inhibitors neostigmine, pyridostigmine and edrophonium, which are mainly used to antagonise non-depolarising neuromuscular blockade in general anaesthesia and in the symptomatic treatment of myasthenia gravis [16].
• 1,3-Dioxane derivative 11 was an extremely potent antagonist of paraoxon-induced toxicity in mice, compared with prototypical protective agents physostigmine and pyridostigmine [17].
• Prolonged effect of succinylcholine after neostigmine and pyridostigmine administration in patients with renal failure [18].

Biological context of pyridostigmine

• Patients with myasthenia who were receiving continuous therapy with oral pyridostigmine had AUC values per unit dose corresponding to those in healthy subjects [19].
• Despite this similarity, there were in general considerable interindividual differences in the bioavailability of pyridostigmine in myasthenic patients [20].
• The pharmacokinetics of pyridostigmine [21].
• Pyridostigmine kinetics with and without renal function [22].
• Pyridostigmine (120 mg, orally) induced a significant (P < 0.01) rise in basal plasma CGRP, while it reduced systolic and diastolic blood pressure [23].

Anatomical context of pyridostigmine

• Because previous animal studies have shown stress-induced disruption of the blood-brain barrier, an alternative possibility was that the stress situation associated with war allowed pyridostigmine penetration into the brain [11].
• The actions of pyridostigmine (Pyr), an anticholinesterase agent, were studied on the acetylcholine (ACh) receptor-ion channel complex and on the electrically excitable membrane of the frog cutaneous pectoris and sartorius muscles and the chronically denervated soleus muscle of the rat [24].
• Neuromuscular junction abnormalities and decreased IGF-I levels may respond to the anticholinesterase pyridostigmine, with consequent improvement in strength, fatigue, and quality of life [25].
• Pyridostigmine reduces somatostatin release from the hypothalamus by increasing central cholinergic neurotransmission [26].
• Pyridostigmine was transferred to the child and accumulated in the amniotic fluid [27].

Associations of pyridostigmine with other chemical compounds

• Therefore, only GHRH combined with PD or ARG may be able to clearly differentiate normal children from patients with GH deficiency, though a normal GH response to these tests cannot rule out the existence of GH hyposecretory state because of hypothalamic dysfunction [28].
• In other experiments, the administration of propranolol (PRO; 40 mg, orally), or clonidine (CLO; 0.300 mg, orally), or pyridostigmine (PD; 120 mg, orally) was followed by GHRH administration 60 min later [29].
• PD increased (P < 0.05) GH (change in area under curves, mean +/- SEM, 790.9 +/- 229.3 microg(*)min/liter) but did not modify insulin and glucose levels [30].
• After nocturnal DEX administration, both PRO and CLO, but not PD, were able to reverse the inhibitory effect of DEX on GHRH-elicited GH release (peaks: 39 +/- 5.5, 25.9 +/- 3.9 and 12.9 +/- 3.1, micrograms/L; DEX + PRO, DEX + CLO, and DEX + PD, respectively) [29].
• Multiple regression analysis also revealed a significant positive correlation between progesterone levels and GH response to pyridostigmine (P less than 0.02) [31].

Gene context of pyridostigmine

• In contrast, pretreatment with yohimbine significantly (P less than 0.05) blunted the pyridostigmine-induced enhancement of GHRH-elicited GH release [32].
• Conversely, preincubation of CYP3A4 with pyridostigmine bromide increased metabolite levels of 6beta-OHTST and 2beta-OHTST [33].
• To block lipolysis and hypothalamic somatostatin release, subjects in group B received acipimox, an antilipolytic agent (500 mg), and pyridostigmine, an acetylcholinesterase inhibitor (60 mg), during the 6 h before iv GHRH [34].
• The PD-induced ghrelin peak did not precede that of GH [30].
• The FA1 responses to placebo were not significantly different from the responses to the combination of pyridostigmine and GHRH [35].

Analytical, diagnostic and therapeutic context of pyridostigmine

• Physiologic changes attributable to pyridostigmine that resulted in need for medical attention, discontinuation of the drug, hospitalization, and/or evacuation from Southwest Asia. RESULTS [36].
• The patient improved with chronic administration of pyridostigmine bromide and plasmapheresis [37].
• This demonstrates that failure to achieve adequate serum pyridostigmine levels following oral administration is due to malabsorption rather than to increased rates of tissue uptake, degradation, or excretion of the drug [38].
• Pyridostigmine kinetics were examined under conditions of clinical use as an antagonist of nondepolarizing neuromuscular blockade in anesthetized patients with and without renal function [22].
• Her subsequent response to pyridostigmine and thymectomy confirmed the diagnosis of myasthenia gravis [39].

References