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Lancet (London, England) Mar 1985
Topics: Administration, Oral; Adult; Female; Humans; Physostigmine
PubMed: 2858639
DOI: 10.1016/s0140-6736(85)91353-4 -
Lancet (London, England) Sep 1980
Topics: Adolescent; Female; Humans; Male; Parasympatholytics; Physostigmine
PubMed: 6106766
DOI: No ID Found -
Toxicology Jun 1999The acute toxicity of organophosphorus (OP) compounds in mammals is due to their irreversible inhibition of acetylcholinesterase (AChE) in the nervous system, which...
The acute toxicity of organophosphorus (OP) compounds in mammals is due to their irreversible inhibition of acetylcholinesterase (AChE) in the nervous system, which leads to increased synaptic acetylcholine levels. The protective actions of intravenously (i.v.) administered pyridostigmine, physostigmine, eptastigmine, and an organophosphate hydrolase, phosphotriesterase, in acute sarin intoxication were studied in mice. The acute intragastric (i.g.) toxicity (LD50) of sarin with and without the pretreatments was tested by the up-and-down method. The mice received pyridostigmine (0.06 mg/kg body weight), physostigmine (0.09 mg/kg body weight), the physostigmine derivative eptastigmine (0.90 mg/kg body weight) or phosphotriesterase (104 U/g, 10.7 microg/g body weight) 10 min prior to the i.g. administration of sarin. Physostigmine was also administered with phosphotriesterase. Phosphotriesterase was the most effective antidote in sarin intoxication. The LD50 value for sarin increased 3.4-fold in mice receiving phosphotriesterase. Physostigmine was the most effective carbamate in sarin exposure. The protective ratios of physostigmine and pyridostigmine were 1.5- and 1.2-1.3-fold, respectively. Eptastigmine did not give any protection against sarin toxicity. Both the phosphotriesterase and physostigmine treatments protected the brain AChE activities measured 24 h after sarin exposure. In phosphotriesterase and physostigmine-treated mice, a 4- and 2-fold higher sarin dose, respectively, was needed to cause a 50% inhibition of brain AChE activity. Moreover, the combination of phosphotriesterase-physostigmine increased the LD50 value for sarin 4.3-fold. The animals pretreated with phosphotriesterase-ephysostigmine tolerated four times the lethal dose in control animals, furthermore their survival time was 2-3 h in comparison to 20 min in controls. In conclusion, phosphotriesterase and physostigmine were the most effective treatments against sarin intoxication. However, eptastigmine did not provide any protection against sarin toxicity.
Topics: Animals; Antidotes; Aryldialkylphosphatase; Esterases; Lethal Dose 50; Male; Mice; Physostigmine; Pyridostigmine Bromide; Sarin
PubMed: 10403635
DOI: 10.1016/s0300-483x(99)00029-3 -
Current Eye Research Nov 1997To investigate if part of the progressive reduction of intraocular pressure (IOP), seen when physostigmine is applied on alternate hours, is due to a reduced aqueous... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
PURPOSE
To investigate if part of the progressive reduction of intraocular pressure (IOP), seen when physostigmine is applied on alternate hours, is due to a reduced aqueous flow.
METHODS
In a randomized, open study, one drop of physostigmine salicylate, 8 mg/ml, was instilled at 7 AM in one randomly assigned eye in each of twenty healthy volunteers. Instillations were repeated on alternate hours throughout the day. Each subject's untreated eye served as control. Fluorophotometry of the anterior segment was performed hourly between 7 Am and 8 PM and aqueous flow was calculated. Subsequently, the subjects underwent tomography and tonometry. The change in anterior chamber depth and volume induced by physostigmine was assessed separately.
RESULTS
The mean aqueous flow during the day was 25-28% higher in the physostigmine-treated eye than in the control eye. The difference was statistically significant from 9 AM (p < 0.05-p < 0.001). Each dose caused a further increase. The mean outflow facility increased by 0.14 microliters/min/mm Hg with 95% confidence interval (CI) 0.09-0.18. Although the increase in outflow facility was small, there was a marked reduction of IOP with a mean difference between treated and untreated eye of 3.2 mm Hg (95% CI: 2.3-4.0).
CONCLUSIONS
Repeated administrations of physostigmine increase the aqueous flow and outflow facility. The combined effect is a marked reduction of IOP.
Topics: Adult; Anterior Chamber; Aqueous Humor; Cholinesterase Inhibitors; Eye; Female; Fluorophotometry; Humans; Intraocular Pressure; Male; Ophthalmic Solutions; Physostigmine
PubMed: 9395778
DOI: 10.1076/ceyr.16.11.1166.5097 -
The Journal of Pediatrics Dec 1975
Topics: Antidepressive Agents, Tricyclic; Antidotes; Diazepam; Humans; Physostigmine; Seizures
PubMed: 1185381
DOI: 10.1016/s0022-3476(75)80946-2 -
Angewandte Chemie (International Ed. in... Jan 2014Physostigmine is a parasympathomimetic drug used to treat a variety of neurological disorders, including Alzheimer's disease and glaucoma. Because of its potent...
Physostigmine is a parasympathomimetic drug used to treat a variety of neurological disorders, including Alzheimer's disease and glaucoma. Because of its potent biological activity and unique pyrroloindole skeleton, physostigmine has been the target of many organic syntheses. However, the biosynthesis of physostigmine has been relatively understudied. In this study, we identified a biosynthetic gene cluster for physostigmine by genome mining. The 8.5 kb gene cluster encodes eight proteins (PsmA-H), seven of which are required for the synthesis of physostigmine from 5-hydroxytryptophan, as shown by in vitro total reconstitution. Further genetic and enzymatic studies enabled us to delineate the biosynthetic pathway for physostigmine. The pathway features an unusual reaction cascade consisting of highly coordinated methylation and acetylation/deacetylation reactions.
Topics: Acetylation; Biological Products; Genomics; Multigene Family; Physostigmine
PubMed: 24227628
DOI: 10.1002/anie.201308069 -
The New England Journal of Medicine Nov 1985
Topics: Administration, Oral; Adult; Biological Availability; Humans; Physostigmine
PubMed: 4058515
DOI: 10.1056/NEJM198511143132016 -
Annals of Internal Medicine Jul 1979Under randomized double-blind conditions, 1.00 to 1.67 mg of intravenous physostigmine (Antilirium) reversed sleep induced by administration of 0.102 to 0.238 mg/kg body... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Under randomized double-blind conditions, 1.00 to 1.67 mg of intravenous physostigmine (Antilirium) reversed sleep induced by administration of 0.102 to 0.238 mg/kg body weight of intravenous diazepam in eight healthy human volunteers. Awakening occurred 330 to 740s after initiation of the physostigmine infusion at a rate of 0.5 mg/min every 4 min. Diazepam plasma levels were not significantly different at the start of either the physostigmine or placebo infusion. Physostigmine did not effect plasma binding of diazepam. Six subjects experienced nausea, and one subject developed an arrhythmia. Physostigmine reverses diazepam-induced hypnosis but causes side-effects requiring cautious administration.
Topics: Adult; Clinical Trials as Topic; Confusion; Diazepam; Double-Blind Method; Humans; Hypnosis; Male; Middle Aged; Physostigmine; Placebos; Random Allocation; Sleep; Time Factors
PubMed: 380427
DOI: 10.7326/0003-4819-91-1-53 -
The Journal of Emergency Medicine 1993
Topics: Humans; Orphenadrine; Physostigmine
PubMed: 8445195
DOI: No ID Found -
The American Journal of Psychiatry Mar 1984
Topics: Depressive Disorder; Dexamethasone; Humans; Hydrocortisone; Methoxyhydroxyphenylglycol; Physostigmine
PubMed: 6703121
DOI: 10.1176/ajp.141.3.aj1413469