physostigmine

Summary

Summary: A cholinesterase inhibitor that is rapidly absorbed through membranes. It can be applied topically to the conjunctiva. It also can cross the blood-brain barrier and is used when central nervous system effects are desired, as in the treatment of severe anticholinergic toxicity.

Top Publications

  1. Wang L, Chaw C, Yang Y, Moochhala S, Zhao B, Ng S, et al. Preparation, characterization, and in vitro evaluation of physostigmine-loaded poly(ortho ester) and poly(ortho ester)/poly(D,L-lactide-co-glycolide) blend microspheres fabricated by spray drying. Biomaterials. 2004;25:3275-82 pubmed
    The physostigmine-loaded poly(ortho ester) (POE), poly(dl-lactide-co-glycolide) (PLGA) and POE/PLGA blend microspheres were fabricated by a spray drying technique...
  2. Kim Y, Lee Y, Kim D, Jung M, Lee C. Scopolamine-induced learning impairment reversed by physostigmine in zebrafish. Neurosci Res. 2010;67:156-61 pubmed publisher
    In this study, the effects of scopolamine, an acetylcholine muscarinic receptor antagonist, and physostigmine, an acetylcholinesterase inhibitor, on the learning ability and memory of zebrafish were evaluated using a passive avoidance ..
  3. Maccecchini M, Chang M, Pan C, John V, Zetterberg H, Greig N. Posiphen as a candidate drug to lower CSF amyloid precursor protein, amyloid-? peptide and ? levels: target engagement, tolerability and pharmacokinetics in humans. J Neurol Neurosurg Psychiatry. 2012;83:894-902 pubmed publisher
  4. Xie G, Deschamps A, Backman S, Fiset P, Chartrand D, Dagher A, et al. Critical involvement of the thalamus and precuneus during restoration of consciousness with physostigmine in humans during propofol anaesthesia: a positron emission tomography study. Br J Anaesth. 2011;106:548-57 pubmed publisher
    ..However, functional imaging changes may result from drug effects unrelated to hypnosis. Establishing a causal link with loss of consciousness is thus difficult...
  5. Jafari Sabet M. NMDA receptor blockers prevents the facilitatory effects of post-training intra-dorsal hippocampal NMDA and physostigmine on memory retention of passive avoidance learning in rats. Behav Brain Res. 2006;169:120-7 pubmed
    ..antagonists, on memory retention of passive avoidance learning was measured in the presence and absence of physostigmine in rats...
  6. Bolourchian N, Hadidi N, Foroutan S, Shafaghi B. Development and optimization of a sublingual tablet formulation for physostigmine salicylate. Acta Pharm. 2009;59:301-12 pubmed publisher
    This study is aimed to design and optimize a sublingual tablet formulation of physostigmine salicylate, an effective drug in Alzheimer's disease and nerve gas poisoning, by means of the D-optimal experimental design methodology...
  7. Utsuki T, Yu Q, Davidson D, Chen D, Holloway H, Brossi A, et al. Identification of novel small molecule inhibitors of amyloid precursor protein synthesis as a route to lower Alzheimer's disease amyloid-beta peptide. J Pharmacol Exp Ther. 2006;318:855-62 pubmed
    ..Translation of APP and A beta actions to mice was demonstrated with one agent. They thus represent interesting lead molecules for assessment in animal models, to define their tolerance and utility as potential AD therapeutics...
  8. Di Cesare Mannelli L, Bartolini A, Ghelardini C. Neuropathy-induced apoptosis: protective effect of physostigmine. J Neurosci Res. 2009;87:1871-6 pubmed publisher
    ..In this model, the acetylcholinesterase inhibitor physostigmine is administered at 0.125 mg/kg i.p. (twice per day) starting from the operation and for 15 days after...
  9. Lahiri D, Chen D, Maloney B, Holloway H, Yu Q, Utsuki T, et al. The experimental Alzheimer's disease drug posiphen [(+)-phenserine] lowers amyloid-beta peptide levels in cell culture and mice. J Pharmacol Exp Ther. 2007;320:386-96 pubmed
    ..Posiphen, like phenserine, can lower Abeta via multiple mechanisms and represents an interesting drug candidate for AD treatment...

More Information

Publications61

  1. Zhao Q, Tang X. Effects of huperzine A on acetylcholinesterase isoforms in vitro: comparison with tacrine, donepezil, rivastigmine and physostigmine. Eur J Pharmacol. 2002;455:101-7 pubmed
    Five inhibitors of acetylcholinesterase, huperzine A, donepezil, tacrine, rivastigmine and physostigmine, were compared with regard to their effects on different molecular forms of acetylcholinesterase in cerebral cortex, hippocampus, ..
  2. Frascogna N. Physostigmine: is there a role for this antidote in pediatric poisonings?. Curr Opin Pediatr. 2007;19:201-5 pubmed
    ..Toxicity may result in symptoms such as severe agitation requiring physical restraint. Physostigmine, an antidote for anticholinergic poisoning, could be useful in this situation...
  3. Freo U, Ricciardi E, Pietrini P, Schapiro M, Rapoport S, Furey M. Pharmacological modulation of prefrontal cortical activity during a working memory task in young and older humans: a PET study with physostigmine. Am J Psychiatry. 2005;162:2061-70 pubmed
    ..The current study was designed to determine how healthy aging influences the neural response to working memory before and during pharmacological potentiation of the cholinergic system...
  4. Bitzinger D, Zausig Y, Paech C, Gruber M, Busse H, Sinner B, et al. Modulation of immune functions in polymorphonuclear neutrophils induced by physostigmine, but not neostigmine, independent of cholinergic neurons. Immunobiology. 2013;218:1049-54 pubmed publisher
    ..We investigated the concentration-response-effects of physostigmine and neostigmine on the oxidative burst activity (human and rat PMN) and the expression of adhesion molecules ..
  5. Pires W, Wanner S, La Guardia R, Rodrigues L, Silveira S, Coimbra C, et al. Intracerebroventricular physostigmine enhances blood pressure and heat loss in running rats. J Physiol Pharmacol. 2007;58:3-17 pubmed
    ..T(tail)), core temperature and blood pressure were measured after injection of 2 microL of 5x10(-3) M physostigmine (Phy; n = 8) or 0.15 M NaCl solution (Sal; n = 8) into the lateral cerebral ventricle...
  6. Marutle A, Ohmitsu M, Nilbratt M, Greig N, Nordberg A, Sugaya K. Modulation of human neural stem cell differentiation in Alzheimer (APP23) transgenic mice by phenserine. Proc Natl Acad Sci U S A. 2007;104:12506-11 pubmed
  7. Militante J, Ma B, Akk G, Steinbach J. Activation and block of the adult muscle-type nicotinic receptor by physostigmine: single-channel studies. Mol Pharmacol. 2008;74:764-76 pubmed publisher
    The plant-derived acetylcholinesterase inhibitor physostigmine has previously been shown to act on the nicotinic acetylcholine receptor (nAChR) causing either direct activation or potentiation of currents elicited by low concentrations ..
  8. Li X, Li J, Zhu X, Cui R, Jiao J. Effects of physostigmine on the conditioned hyperactivity and locomotor sensitization to morphine in rats. Behav Brain Res. 2010;206:223-8 pubmed publisher
    ..measures conditioned hyperactivity and locomotor sensitization, and then investigated the effects of physostigmine on the development and expression of conditioned hyperactivity and locomotor sensitization in rats...
  9. Wüppen K, Oesterle D, Lewicka S, Kopitz J, Plaschke K. A subchronic application period of glucocorticoids leads to rat cognitive dysfunction whereas physostigmine induces a mild neuroprotection. J Neural Transm (Vienna). 2010;117:1055-65 pubmed publisher
    ..The goal of this study was to investigate whether or not repeated applications of physostigmine over 3 days lead to protective effects on rat spatial cognitive abilities in contrast to the deteriorating ..
  10. Joosen M, Smit A, van Helden H. Treatment efficacy in a soman-poisoned guinea pig model: added value of physostigmine?. Arch Toxicol. 2011;85:227-37 pubmed publisher
    ..The model allowed the determination of the therapeutic effects at the short-term of obidoxime, atropine and physostigmine. Obidoxime exerted the highest therapeutic efficacy at administration of the lowest dose (3.1 mg/kg i.m...
  11. Woodruff Pak D, Ewers M, Shiotani T, Watabe S, Tanaka M, Wenk G. Nefiracetam and physostigmine: separate and combined effects on learning in older rabbits. Neurobiol Aging. 2004;25:807-16 pubmed
    b>Physostigmine and nefiracetam were tested alone and in combination in 104 rabbits with a mean age of 28 months conditioned in the 750 ms delay eyeblink classical conditioning procedure. In Experiment 1, five doses of physostigmine (0...
  12. Choi E, Park D, Yon J, Hur G, Ha Y, Che J, et al. Protection by sustained release of physostigmine and procyclidine of soman poisoning in rats. Eur J Pharmacol. 2004;505:83-91 pubmed
    ..implanted subcutaneously with osmotic minipumps containing the combinational prophylactic regimen composed of physostigmine, a reversible cholinesterase inhibitor, and procyclidine, an N-methyl-D-aspartate antagonist possessing ..
  13. Khosravani N, Birkhed D, Ekström J. The cholinesterase inhibitor physostigmine for the local treatment of dry mouth: a randomized study. Eur J Oral Sci. 2009;117:209-17 pubmed publisher
    Application of physostigmine to the oromucosal surface with the aim of stimulating underlying mucin-producing glands while reducing cholinergic systemic effects might be a strategy for treating dry mouth...
  14. Monteiro M, Quintaneiro C, Morgado F, Soares A, Guilhermino L. Characterization of the cholinesterases present in head tissues of the estuarine fish Pomatoschistus microps: application to biomonitoring. Ecotoxicol Environ Saf. 2005;62:341-7 pubmed
    ..microps was determined. The results suggest the presence of two types of ChE in the whole-head homogenate. The present study underscores the relevance of ChE characterization before its use as a biomarker in biomonitoring studies...
  15. Bentley P, Vuilleumier P, Thiel C, Driver J, Dolan R. Cholinergic enhancement modulates neural correlates of selective attention and emotional processing. Neuroimage. 2003;20:58-70 pubmed
    ..and emotionality to examine regions showing effects of cholinergic modulation by the anticholinesterase physostigmine. Either face or house pictures appeared at task-relevant locations, with the alternative picture type at ..
  16. Peter C, Schmidt K, Hofer S, Stephan M, Martin E, Weigand M, et al. Effects of physostigmine on microcirculatory alterations during experimental endotoxemia. Shock. 2010;33:405-11 pubmed publisher
    ..By inhibition of the cholinesterase, physostigmine increases acetylcholine and induces the cholinergic anti-inflammatory pathway...
  17. Kutsuna S, Tsuruta R, Fujita M, Todani M, Yagi T, Ogino Y, et al. Cholinergic agonist physostigmine suppresses excessive superoxide anion radical generation in blood, oxidative stress, early inflammation, and endothelial injury in rats with forebrain ischemia/reperfusion. Brain Res. 2010;1313:242-9 pubmed publisher
    ..In this study, we investigated the effects of the cholinergic agonist, physostigmine, on jugular venous superoxide radical (O(2)(-)) generation, oxidative stress, early inflammation, and ..
  18. Bansal I, Waghmare C, Anand T, Gupta A, Bhattacharya B. Differential mRNA expression of acetylcholinesterase in the central nervous system of rats with acute and chronic exposure of sarin & physostigmine. J Appl Toxicol. 2009;29:386-94 pubmed publisher
    ..AChE) gene expression in the brain of female rats exposed to different doses of sarin and physostigmine. Short-term effects were studied with an acute single subcutaneous dose (s.c.) of 80 microg kg(-1) (0...
  19. Chaw C, Tan C, Yang Y, Wang L, Moochhala S. Design of physostigmine-loaded polymeric microparticles for pretreatment against exposure to organophosphate agents. Biomaterials. 2003;24:1271-7 pubmed
    b>Physostigmine is an anti-cholinesterase used for the pretreatment of a poisoning caused by highly toxic organophosphorus neurotoxins...
  20. Zhan Z, Bian H, Wang J, Shan W. Synthesis of physostigmine analogues and evaluation of their anticholinesterase activities. Bioorg Med Chem Lett. 2010;20:1532-4 pubmed publisher
    A series of physostigmine analogues were prepared and evaluated for cholinesterase inhibition activities, including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)...
  21. Winblad B, Giacobini E, Frolich L, Friedhoff L, Bruinsma G, Becker R, et al. Phenserine efficacy in Alzheimer's disease. J Alzheimers Dis. 2010;22:1201-8 pubmed publisher
  22. Gard P, Naylor C, Ali S, Partington C. Blockade of pro-cognitive effects of angiotensin IV and physostigmine in mice by oxytocin antagonism. Eur J Pharmacol. 2012;683:155-60 pubmed publisher
    ..This study explored the role of oxytocin in the cognitive effects of angiotensin IV with physostigmine as a control and used isolated smooth muscle to assess the pharmacological selectivity of the observed ..
  23. Beilin B, Bessler H, Papismedov L, Weinstock M, Shavit Y. Continuous physostigmine combined with morphine-based patient-controlled analgesia in the postoperative period. Acta Anaesthesiol Scand. 2005;49:78-84 pubmed
    ..b>Physostigmine is a cholinesterase inhibitor, which crosses the blood-brain barrier and elevates brain acetylcholine level...
  24. Suchard J. Assessing physostigmine's contraindication in cyclic antidepressant ingestions. J Emerg Med. 2003;25:185-91 pubmed
    ..of the electrocardiographic QRS interval are commonly considered as contraindications to the use of physostigmine as an antidote for antimuscarinic toxicity...
  25. Plourde G, Chartrand D, Fiset P, Font S, Backman S. Antagonism of sevoflurane anaesthesia by physostigmine: effects on the auditory steady-state response and bispectral index. Br J Anaesth. 2003;91:583-6 pubmed
    b>Physostigmine, a centrally acting anticholinesterase, antagonizes the hypnotic effect of propofol, as shown by the return of consciousness (response to commands) or wakefulness (spontaneous eye-opening without response to commands) and ..
  26. Huang X, Lee B, Johnson G, Naleway J, Guzikowski A, Dai W, et al. Novel assay utilizing fluorochrome-tagged physostigmine (Ph-F) to in situ detect active acetylcholinesterase (AChE) induced during apoptosis. Cell Cycle. 2005;4:140-7 pubmed
    ..enzyme in live intact cells and be applicable to fluorescence microscopy and cytometry, the fluorescein-tagged physostigmine (Ph-F), high affinity ligand (inhibitor) reactive with the active center of AChE, was constructed and tested ..
  27. Li X, Spence J, Buhner D, Hart J, Cullum C, Biggs M, et al. Hippocampal dysfunction in Gulf War veterans: investigation with ASL perfusion MR imaging and physostigmine challenge. Radiology. 2011;261:218-25 pubmed publisher
    To determine, with arterial spin labeling (ASL) perfusion magnetic resonance (MR) imaging and physostigmine challenge, if abnormal hippocampal blood flow in ill Gulf War veterans persists 11 years after initial testing with single photon ..
  28. Wu H, Chang C, Cheng K, Chang C, Yeh C, Cheng J. Increase of plasma insulin by racecadotril, an inhibitor of enkephalinase, in Wistar rats. Horm Metab Res. 2010;42:261-7 pubmed publisher
    ..Our results suggested that racecadotril increased insulin secretion to lower blood glucose mainly via regulation of parasympathetic tone in Wistar rats...
  29. Ul Haq Z, Mahmood U, Jehangir B. Ligand-based 3D-QSAR studies of physostigmine analogues as acetylcholinesterase inhibitors. Chem Biol Drug Des. 2009;74:571-81 pubmed publisher
    Natural alkaloid Physostigmine is one of the most potent pseudo-irreversible inhibitor of Acetylcholinesterase...
  30. Venti A, Giordano T, Eder P, Bush A, Lahiri D, Greig N, et al. The integrated role of desferrioxamine and phenserine targeted to an iron-responsive element in the APP-mRNA 5'-untranslated region. Ann N Y Acad Sci. 2004;1035:34-48 pubmed
    ..Phenserine was most efficient to block translation under conditions of intracellular iron chelation with desferrioxamine suggesting that this anticholinesterase operated through an iron (metal)-dependent pathway at the APP 5'-UTR site...
  31. Greig N, Sambamurti K, Yu Q, Brossi A, Bruinsma G, Lahiri D. An overview of phenserine tartrate, a novel acetylcholinesterase inhibitor for the treatment of Alzheimer's disease. Curr Alzheimer Res. 2005;2:281-90 pubmed
    ..Novel drug design studies have focused on the classical ChE inhibitor, (-)-physostigmine, producing alterations in chemical composition and three-dimensional structure, which may offer an improved ..
  32. Hofer S, Eisenbach C, Lukic I, Schneider L, Bode K, Brueckmann M, et al. Pharmacologic cholinesterase inhibition improves survival in experimental sepsis. Crit Care Med. 2008;36:404-8 pubmed
    ..Here we studied whether the cholinergic anti-inflammatory pathway can be activated by pharmacologic cholinesterase inhibition in vivo...
  33. Hedner J, Kraiczi H, Peker Y, Murphy P. Reduction of sleep-disordered breathing after physostigmine. Am J Respir Crit Care Med. 2003;168:1246-51 pubmed
    The cholinesterase inhibitor physostigmine (PHYS) was investigated in a double-blind, placebo-controlled, randomized, crossover trial of 10 male patients with moderate to severe obstructive sleep apnea. PHYS (0...
  34. Jameson R, Seidler F, Qiao D, Slotkin T. Chlorpyrifos affects phenotypic outcomes in a model of mammalian neurodevelopment: critical stages targeting differentiation in PC12 cells. Environ Health Perspect. 2006;114:667-72 pubmed
  35. Kadir A, Andreasen N, Almkvist O, Wall A, Forsberg A, Engler H, et al. Effect of phenserine treatment on brain functional activity and amyloid in Alzheimer's disease. Ann Neurol. 2008;63:621-31 pubmed publisher
  36. Cho Y, Kim W, Hur G, Ha Y. Minimum effective drug concentrations of a transdermal patch system containing procyclidine and physostigmine for prophylaxis against soman poisoning in rhesus monkeys. Environ Toxicol Pharmacol. 2012;33:1-8 pubmed publisher
    ..containing procyclidine, an N-methyl-d-aspartate receptor antagonist possessing anticholinergic action, and physostigmine, a reversible cholinesterase inhibitor, was developed, and its prophylactic efficacy against soman ..
  37. Yu Q, Holloway H, Luo W, Lahiri D, Brossi A, Greig N. Long-acting anticholinesterases for myasthenia gravis: synthesis and activities of quaternary phenylcarbamates of neostigmine, pyridostigmine and physostigmine. Bioorg Med Chem. 2010;18:4687-93 pubmed publisher
    ..An extended duration of cholinesterase inhibition was determined in rodent, making them of potential interest as long-acting agents for myasthenia gravis...
  38. Hunsaker M, Rogers J, Kesner R. Behavioral characterization of a transection of dorsal CA3 subcortical efferents: comparison with scopolamine and physostigmine infusions into dorsal CA3. Neurobiol Learn Mem. 2007;88:127-36 pubmed
    ..In Experiment 1, physostigmine and scopolamine (both 0...
  39. Thal L, Fuld P, Masur D, Sharpless N. Oral physostigmine and lecithin improve memory in Alzheimer disease. Ann Neurol. 1983;13:491-6 pubmed
    Eight patients with early Alzheimer disease were treated with gradually increasing multiple daily doses of oral physostigmine and supplemental lecithin...
  40. Al Jafari A, Kamal M, Greig N, Alhomida A, Perry E. Kinetics of human erythrocyte acetylcholinesterase inhibition by a novel derivative of physostigmine: phenserine. Biochem Biophys Res Commun. 1998;248:180-5 pubmed
  41. Horn E, Standl T, Sessler D, Von Knobelsdorff G, Buchs C, Schulte Am Esch J. Physostigmine prevents postanesthetic shivering as does meperidine or clonidine. Anesthesiology. 1998;88:108-13 pubmed
    ..Cholinergic stimulation of the hypothalamic-pituitary-adrenal axis and adrenal medulla by physostigmine enhances secretion of arginine vasopressin, epinephrine, and norepinephrine...
  42. Furey M, Pietrini P, Haxby J. Cholinergic enhancement and increased selectivity of perceptual processing during working memory. Science. 2000;290:2315-9 pubmed
    ..We studied the effect of the cholinesterase inhibitor physostigmine on subcomponents of this complex function...
  43. Shaw K, Utsuki T, Rogers J, Yu Q, Sambamurti K, Brossi A, et al. Phenserine regulates translation of beta -amyloid precursor protein mRNA by a putative interleukin-1 responsive element, a target for drug development. Proc Natl Acad Sci U S A. 2001;98:7605-10 pubmed
    ..This study identifies an approach for the regulation of betaAPP expression that can result in a substantial reduction in the level of Abeta...
  44. Sarkar S, Thomas B, Muralikrishnan D, Mohanakumar K. Effects of serotoninergic drugs on tremor induced by physostigmine in rats. Behav Brain Res. 2000;109:187-93 pubmed
    We investigated the effects of various serotoninergic drugs and serotonin (5-HT) depletion on physostigmine-induced visible tremor in rats. Physostigmine (0.25-1...
  45. Ebert U, Oertel R, Kirch W. Physostigmine reversal of midazolam-induced electroencephalographic changes in healthy subjects. Clin Pharmacol Ther. 2000;67:538-48 pubmed
    Midazolam is a water-soluble benzodiazepine. Flumazenil is a potent antagonist of midazolam-induced sedation. Physostigmine has also been shown to reverse benzodiazepine sedation in anecdotal reports...
  46. Rubin R, O Toole S, Rhodes M, Sekula L, Czambel R. Hypothalamo-pituitary-adrenal cortical responses to low-dose physostigmine and arginine vasopressin administration: sex differences between major depressives and matched control subjects. Psychiatry Res. 1999;89:1-20 pubmed
    ..To test the hypothesis of increased cholinergic sensitivity in major depression, physostigmine (PHYSO), a reversible cholinesterase inhibitor, was administered to patients and control subjects at a dose ..
  47. Poyhia R, Xu M, Kontinen V, Paananen S, Kalso E. Systemic physostigmine shows antiallodynic effects in neuropathic rats. Anesth Analg. 1999;89:428-33 pubmed
    ..aim of this study was to examine the antiallodynic and antinociceptive effects of subcutaneously administered physostigmine (50, 100, 200 micrograms/kg), compared with morphine (2...
  48. Furey M, Pietrini P, Alexander G, Mentis M, Szczepanik J, Shetty U, et al. Time course of pharmacodynamic and pharmacokinetic effects of physostigmine assessed by functional brain imaging in humans. Pharmacol Biochem Behav. 2000;66:475-81 pubmed
    ..and pharmacodynamics, including butyrylcholinesterase inhibition and central neural responses, of physostigmine in healthy young subjects...
  49. Mehta H, Thomas B, Mohanakumar K. Effects of p-chlorophenylalanine on striatal acetylcholinesterase activity and on biogenic amine levels in nuclei raphe and caudate-putamen during physostigmine-induced tremor in rats. Neurosci Lett. 2001;299:105-8 pubmed
    ..depletor, on the neurochemical processes in nuclei raphe dorsalis (NRD) and caudatus putamen (NCP) paralleling physostigmine-induced tremor in rats...
  50. Yu Q, Holloway H, Flippen Anderson J, Hoffman B, Brossi A, Greig N. Methyl analogues of the experimental Alzheimer drug phenserine: synthesis and structure/activity relationships for acetyl- and butyrylcholinesterase inhibitory action. J Med Chem. 2001;44:4062-71 pubmed
    ..we have synthesized a series of novel analogues of the potent anticholinesterases phenserine (2) and physostigmine (1)...
  51. Wang G, Fowler S. Concurrent quantification of tremor and depression of locomotor activity induced in rats by harmaline and physostigmine. Psychopharmacology (Berl). 2001;158:273-80 pubmed
    Both harmaline and physostigmine are known to produce whole-body tremors in rodents, yet there is little quantitative information on the differential frequency characteristics of these tremors or on other possible motor effects of these ..
  52. Hoffmann K, Wirmer A, Kunst M, Gocht D, Heinrich R. Muscarinic excitation in grasshopper song control circuits is limited by acetylcholinesterase activity. Zoolog Sci. 2007;24:1028-35 pubmed