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JACEP Jun 1976Physostigmine salicylate, a cholinesterase inhibitor, has been shown to reverse the effects of certain drugs with anticholinergic properties. The paper provides a brief...
Physostigmine salicylate, a cholinesterase inhibitor, has been shown to reverse the effects of certain drugs with anticholinergic properties. The paper provides a brief historical account of physostigmine, reviews the cholinergic drugs and their effects and suggests a management protocol based on physiologic criteria. Twenty-six overdose cases, recently treated with physostigmine, are summarized. The controversy regarding the etiology of seizures following physostigmine administration is discussed.
Topics: Cholinesterase Inhibitors; Dose-Response Relationship, Drug; Humans; Physostigmine; Poisoning; Substance-Related Disorders
PubMed: 933411
DOI: 10.1016/s0361-1124(76)80253-5 -
JACEP Feb 1976Physostigmine salicylate, a centrally acting cholinesterase inhibitor, is effective in rapidly and dramatically reversing the effects produced by anticholinergic drugs....
Physostigmine salicylate, a centrally acting cholinesterase inhibitor, is effective in rapidly and dramatically reversing the effects produced by anticholinergic drugs. Three case reports of successful use of physostigmine are presented. Since physostigmine is a tertiary amine that allows for passage of the drug into the central nervous system, it can reverse both the peripheral and central nervous system effects of anticholinergic poisoning. The adverse effects and contraindications of physostigmine use are discussed.
Topics: Adult; Female; Humans; Parasympatholytics; Physostigmine
PubMed: 933396
DOI: 10.1016/s0361-1124(76)80192-x -
Anasthesiologie, Intensivmedizin,... Mar 2007The central anticholinergic syndrome should be considered in patients with altered mental status following anaesthesia. Physostigmine, a reversible acetylcholinesterase...
The central anticholinergic syndrome should be considered in patients with altered mental status following anaesthesia. Physostigmine, a reversible acetylcholinesterase inhibitor, is a first-line medicament for the therapy of the central anticholinergic syndrome. Physostigmine crosses the blood-brain barrier and elevates acetylcholine levels in the brain. For prevention of postanaesthetic shivering, for treatment of intoxications and postoperative pain, and for patients suspected of having antimuscarinic delirium physostigmine is also indicated.
Topics: Acetylcholine; Blood-Brain Barrier; Brain; Cholinesterase Inhibitors; Drug Therapy; Humans; Physostigmine; Postoperative Care
PubMed: 17366438
DOI: 10.1055/s-2007-974580 -
Lancet (London, England) Dec 1972
Topics: Humans; Movement Disorders; Physostigmine
PubMed: 4118718
DOI: 10.1016/s0140-6736(72)93003-6 -
Expert Opinion on Investigational Drugs Jul 2007Phenserine, a derivative of physostigmine, was first described as an inhibitor of acetylcholinesterase (AChE) and was shown to improve cognition in various experimental... (Review)
Review
Phenserine, a derivative of physostigmine, was first described as an inhibitor of acetylcholinesterase (AChE) and was shown to improve cognition in various experimental paradigms in rodents and dogs. It was clinically tested for Alzheimer's disease, with moderate success in initial Phase II studies. Phenserine deserves attention for an additional quality of action: in addition to inhibiting AChE, it modulates the amount of beta-amyloid precursor protein (APP) in neuronal cell culture by reducing APP translation. This effect probably involves interaction of phenserine with a regulatory element in the 5'-untranslated region of the APP gene that controls APP expression. Phenserine apparently reduces translational efficiency of APP mRNA into protein, a process that may involve an interaction with iron and/or an iron-responsive element. As a consequence, phenserine reduces beta-amyloid peptide (Abeta) formation in vitro and in vivo. Phenserine is also unique because of differing actions of its enantiomers: (-)-phenserine is the active enantiomer for inhibition of AChE, whereas (+)-phenserine ('posiphen') has weak activity as an AChE inhibitor and can be dosed much higher. Both enantiomers are equipotent in downregulating APP expression. (+)-Posiphen may be a promising drug, either alone or in combination with (-)-phenserine, to attenuate the progression of Alzheimer's disease.
Topics: Alzheimer Disease; Animals; Clinical Trials, Phase II as Topic; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Drug Administration Schedule; Drugs, Investigational; Female; Follow-Up Studies; Humans; Male; Maximum Tolerated Dose; Mice; Physostigmine; Risk Assessment; Sensitivity and Specificity; Treatment Outcome
PubMed: 17594192
DOI: 10.1517/13543784.16.7.1087 -
The Journal of Emergency Medicine 1991
Topics: Antidotes; Humans; Parasympatholytics; Physostigmine
PubMed: 1861064
DOI: 10.1016/0736-4679(91)90426-g -
Journal of the American Medical... Feb 1946
Topics: Arthritis; Arthritis, Rheumatoid; Humans; Nervous System Diseases; Physostigmine; Spasm
PubMed: 21010020
DOI: 10.1001/jama.1946.02870050017004 -
Biomedicine & Pharmacotherapy =... Oct 2019In the context of the cholinergic anti-inflammatory pathway, the clinical trial Anticholium® per Se (EudraCT Number: 2012-001650-26, ClinicalTrials.gov NCT03013322)... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In the context of the cholinergic anti-inflammatory pathway, the clinical trial Anticholium® per Se (EudraCT Number: 2012-001650-26, ClinicalTrials.gov NCT03013322) addressed the possibility of taking adjunctive physostigmine salicylate treatment in septic shock from bench to bedside. Pharmacokinetics (PK) are likely altered in critically ill patients; data on physostigmine PK and target concentrations are sparse, particularly for continuous infusion. Our objective was to build a population PK (popPK) model for physostigmine, and further evaluate pharmacodynamics (PD) and concentration-response relationship in this setting.
METHODS
In the randomized, double-blind, placebo-controlled trial, 20 patients with perioperative septic shock either received an initial dose of 0.04 mg/kg physostigmine salicylate, followed by continuous infusion of 1 mg/h for up to 120 h, or equivalent volumes of 0.9% sodium chloride (placebo group). Physostigmine plasma concentrations and acetylcholinesterase (AChE) activity were measured; concentration-response associations were evaluated, and popPK and PD modeling was performed with NONMEM.
RESULTS
Steady state physostigmine plasma concentrations reached 7.60 ± 2.81 ng/mL (mean ± standard deviation [SD]). PK was best described by a two-compartment model with linear clearance. Significant covariate effects were detected for body weight and age on clearance, as well as a high inter-individual variability of the central volume of distribution. AChE activity was significantly reduced to 30.5%-50.6% of baseline activity during physostigmine salicylate infusion. A sigmoidal direct effect PD model best described enzyme inhibition by physostigmine, with an estimated half maximal effective concentration (EC) of 5.99 ng/mL.
CONCLUSIONS
PK of physostigmine in patients with septic shock displayed substantial inter-individual variability with body weight and age influencing the clearance. Physostigmine inhibited AChE activity with a sigmoidal concentration-response effect.
Topics: Aged; Cholinesterases; Female; Humans; Male; Middle Aged; Models, Biological; Physostigmine; Shock, Septic
PubMed: 31398669
DOI: 10.1016/j.biopha.2019.109318 -
Canadian Anaesthetists' Society Journal Nov 1977The effects of physostigmine on reversal of post-operative somnolence following general anaesthesia were evaluated in 187 patients. Significant reversal of...
The effects of physostigmine on reversal of post-operative somnolence following general anaesthesia were evaluated in 187 patients. Significant reversal of anaesthetic-induced post-operative somnolence was observed in those patients receiving physostigmine when compared to a control group. These results suggest that general anaesthesia with halothane may be included in those situations where central nervous system depression may be reversed by administration of physostigmine. Cholinergic side-effects observed with physostigmine administration were minimal.
Topics: Adolescent; Adult; Anesthesia; Humans; Middle Aged; Physostigmine; Sleep; Time Factors
PubMed: 589507
DOI: 10.1007/BF03006714 -
Science (New York, N.Y.) Jul 1978Nineteen normal male subjects received 1.0 milligram of physostigmine or 1.0 milligram of saline by a slow intravenous infusion on two nonconsecutive days. Physostigmine... (Clinical Trial)
Clinical Trial
Nineteen normal male subjects received 1.0 milligram of physostigmine or 1.0 milligram of saline by a slow intravenous infusion on two nonconsecutive days. Physostigmine significantly enhanced storage of information into long-term memory. Retrieval of information from long-term memory was also improved. Short-term memory processes were not significantly altered by physostigmine.
Topics: Acetylcholine; Adolescent; Adult; Alzheimer Disease; Clinical Trials as Topic; Humans; Male; Memory; Memory, Short-Term; Physostigmine
PubMed: 351807
DOI: 10.1126/science.351807