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Showing drug card for Pyridostigmine (DB00545)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:05:49
Primary Accession Number DB00545
Secondary Accession Number
  • APRD00380
Name Pyridostigmine
Drug Type
  • Approved
  • Small Molecule
Description A cholinesterase inhibitor with a slightly longer duration of action than neostigmine. It is used in the treatment of myasthenia gravis and to reverse the actions of muscle relaxants. [PubChem]
Synonyms
  1. Pyridine N-Oxide
  2. Pyridostigmine Bromide
  3. Pyridostigmine Bromine
  4. Pyridostigminum
Brand Names
  1. Mestinon
  2. Mestinon-SR
  3. Regonol
Brand Mixtures Not Available
Chemical IUPAC Name (1-methylpyridin-1-ium-3-yl) N,N-dimethylcarbamate
Chemical Formula C9H13N2O2
Chemical Structure Structure
CAS Registry Number 155-97-5
InChI Identifier InChI=1/C9H13N2O2/c1-10(2)9(12)13-8-5-4-6-11(3)7-8/h4-7H,1-3H3/q+1
InChI Key RVOLLAQWKVFTGE-UHFFFAOYAK
KEGG Drug D00487 Link Image
KEGG Compound C07410 Link Image
PubChem Compound 4991 Link Image
PubChem Substance 9614 Link Image
ChEBI ID Not Available
PharmGKB ID PA451185 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 00869953 Link Image
RxList Link http://www.rxlist.com/cgi/generic2/pyridostigmine.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Pyridostigmine Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Urban, U.S. pat. 2,572,579 (1951 to Hoffmann-La Roche)
Average Molecular Weight 181.2117
Monoisotopic Molecular Weight 181.0977
State Solid
Melting Point 153 oC
Experimental Water Solubility 1.04 mg/mL [Predicted by ALOGPS] Source: PhysProp
Predicted Water Solubility 1.04e+00 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 1.554 Source: PhysProp
Predicted LogP -3.13 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -2.32 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID 1F8U Link Image
Experimental PDB File Show
Experimental PDB Structure
Isomeric SMILES CN(C)C(=O)OC1=C[N+](C)=CC=C1
Canonical SMILES CN(C)C(=O)OC1=C[N+](C)=CC=C1
Drug Category
  • Antimyasthenics
  • Cholinesterase Inhibitors
  • Parasympathomimetics
ATC Codes
AHFS Codes
  • 12:04.00
Indication For the treatment of myasthenia gravis.
Pharmacology Pyridostigmine is a parasympathomimetic and a reversible cholinesterase inhibitor. Since it is a quaternary amine, it is poorly absorbed in the gut and doesn't cross the blood-brain barrier. Pyridostigmine has a slightly longer duration of action than NEOSTIGMINE. It is used in the treatment of myasthenia gravis and to reverse the actions of muscle relaxants.
Mechanism of Action Pyridostigmine inhibits acetylcholinesterase in the synaptic cleft by competing with acetylcholine for attachment to acetylcholinesterase, thus slowing down the hydrolysis of acetylcholine, and thereby increases efficiency of cholinergic transmission in the neuromuscular junction and prolonges the effects of acetylcholine.
Absorption Poorly absorbed from the GI tract with an oral bioavailability of 7.6 +/- 2.4%.
Toxicity Not Available
Protein Binding Not Available
Biotransformation Hydrolysis by cholinesterases and by liver.
Half Life 3 hours following oral administration.
Dosage Forms
Form Route
Tablet Oral
Tablet, extended release Oral
Patient Information Not Available
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Betamethasone The corticosteroid decreases the effect of anticholinesterases
Corticotropin The corticosteroid decreases the effect of anticholinesterases
Cortisone acetate The corticosteroid decreases the effect of anticholinesterases
Cosyntropin The corticosteroid decreases the effect of anticholinesterases
Dexamethasone The corticosteroid decreases the effect of anticholinesterases
Fludrocortisone The corticosteroid decreases the effect of anticholinesterases
Hydrocortisone The corticosteroid decreases the effect of anticholinesterases
Methylprednisolone The corticosteroid decreases the effect of anticholinesterases
Paramethasone The corticosteroid decreases the effect of anticholinesterases
Prednisolone The corticosteroid decreases the effect of anticholinesterases
Prednisone The corticosteroid decreases the effect of anticholinesterases
Succinylcholine The corticosteroid decreases the effect of anticholinesterases
Triamcinolone The corticosteroid decreases the effect of anticholinesterases
Food Interactions
  • Take with food to decrease adverse effects.
Pathways Not Available
General References
  1. Singer W, Opfer-Gehrking TL, McPhee BR, Hilz MJ, Bharucha AE, Low PA: Acetylcholinesterase inhibition: a novel approach in the treatment of neurogenic orthostatic hypotension. J Neurol Neurosurg Psychiatry. 2003 Sep;74(9):1294-8. [PubMed Link Image]
  2. Drugs.com Link Image
  3. Wikipedia Link Image
  4. RxList Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cholinesterase
Targets
  1. Acetylcholinesterase
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cholinesterase
Enzyme 1 Gene Name BCHE
Enzyme 1 SwissProt ID P06276 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >Cholinesterase 
MHSKVTIICIRFLFWFLLLCMLIGKSHTEDDIIIATKNGKVRGMNLTVFGGTVTAFLGIP
YAQPPLGRLRFKKPQSLTKWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDC
LYLNVWIPAPKPKNATVLIWIYGGGFQTGTSSLHVYDGKFLARVERVIVVSMNYRVGALG
FLALPGNPEAPGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESAGAASVSLHLLSPG
SHSLFTRAILQSGSFNAPWAVTSLYEARNRTLNLAKLTGCSRENETEIIKCLRNKDPQEI
LLNEAFVVPYGTPLSVNFGPTVDGDFLTDMPDILLELGQFKKTQILVGVNKDEGTAFLVY
GAPGFSKDNNSIITRKEFQEGLKIFFPGVSEFGKESILFHYTDWVDDQRPENYREALGDV
VGDYNFICPALEFTKKFSEWGNNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPLER
RDNYTKAEEILSRSIVKRWANFAKYGNPNETQNNSTSWPVFKSTEQKYLTLNTESTRIMT
KLRAQQCRFWTSFFPKVLEMTGNIDEAEWEWKAGFHRWNNYMMDWKNQFNDYTSKKESCV
GL
Drug Target 1 [top]
Target 1 ID 474
Target 1 Name Acetylcholinesterase
Target 1 Synonyms
  1. AChE
  2. Acetylcholinesterase precursor
  3. EC 3.1.1.7
Target 1 Gene Name ACHE
Target 1 Protein Sequence >Acetylcholinesterase precursor 
MRPPQCLLHTPSLASPLLLLLLWLLGGGVGAEGREDAELLVTVRGGRLRGIRLKTPGGPV
SAFLGIPFAEPPMGPRRFLPPEPKQPWSGVVDATTFQSVCYQYVDTLYPGFEGTEMWNPN
RELSEDCLYLNVWTPYPRPTSPTPVLVWIYGGGFYSGASSLDVYDGRFLVQAERTVLVSM
NYRVGAFGFLALPGSREAPGNVGLLDQRLALQWVQENVAAFGGDPTSVTLFGESAGAASV
GMHLLSPPSRGLFHRAVLQSGAPNGPWATVGMGEARRRATQLAHLVGCPPGGTGGNDTEL
VACLRTRPAQVLVNHEWHVLPQESVFRFSFVPVVDGDFLSDTPEALINAGDFHGLQVLVG
VVKDEGSYFLVYGAPGFSKDNESLISRAEFLAGVRVGVPQVSDLAAEAVVLHYTDWLHPE
DPARLREALSDVVGDHNVVCPVAQLAGRLAAQGARVYAYVFEHRASTLSWPLWMGVPHGY
EIEFIFGIPLDPSRNYTAEEKIFAQRLMRYWANFARTGDPNEPRDPKAPQWPPYTAGAQQ
YVSLDLRPLEVRRGLRAQACAFWNRFLPKLLSATDTLDEAERQWKAEFHRWSSYMVHWKN
QFDHYSKQDRCSDL
Target 1 Number of Residues 624
Target 1 Molecular Weight 67797
Target 1 Theoretical pI 6.24
Target 1 GO Classification
Function
catalytic activity
hydrolase activity
hydrolase activity, acting on ester bonds
carboxylic ester hydrolase activity
cholinesterase activity
Process
Not Available
Component
Not Available
Target 1 General Function Lipid transport and metabolism
Target 1 Specific Function Rapidly hydrolyzes choline released into the synapse
Target 1 Pathways
Name SMPDB Link KEGG Link
Glycerophospholipid metabolism map00564 Link Image
Target 1 Reactions
  • acetylcholine + H2O = choline + acetate
Target 1 Pfam Domain Function
Target 1 Signals
  • 1-31
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 177975 Link Image
Target 1 UniProtKB/Swiss-Prot ID P22303 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name ACES_HUMAN Link Image
Target 1 PDB ID 1F8U Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Cytoplasmic
Target 1 Gene Sequence >1845 bp 
ATGAGGCCCCCGCAGTGTCTGCTGCACACGCCTTCCCTGGCTTCCCCACTCCTTCTCCTC
CTCCTCTGGCTCCTGGGTGGAGGAGTGGGGGCTGAGGGCCGGGAGGATGCAGAGCTGCTG
GTGACGGTGCGTGGGGGCCGGCTGCGGGGCATTCGCCTGAAGACCCCCGGGGGCCCTGTC
TCTGCTTTCCTGGGCATCCCCTTTGCGGAGCCACCCATGGGACCCCGTCGCTTTCTGCCA
CCGGAGCCCAAGCAGCCTTGGTCAGGGGTGGTAGACGCTACAACCTTCCAGAGTGTCTGC
TACCAATATGTGGACACCCTATACCCAGGTTTTGAGGGCACCGAGATGTGGAACCCCAAC
CGTGAGCTGAGCGAGGACTGCCTGTACCTCAACGTGTGGACACCATACCCCCGGCCTACA
TCCCCCACCCCTGTCCTCGTCTGGATCTATGGGGGTGGCTTCTACAGTGGGGCCTCCTCC
TTGGACGTGTACGATGGCCGCTTCTTGGTACAGGCCGAGAGGACTGTGCTGGTGTCCATG
AACTACCGGGTGGGAGCCTTTGGCTTCCTGGCCCTGCCGGGGAGCCGAGAGGCCCCGGGC
AATGTGGGTCTCCTGGATCAGAGGCTGGCCCTGCAGTGGGTGCAGGAGAACGTGGCAGCC
TTCGGGGGTGACCCGACATCAGTGACGCTGTTTGGGGAGAGCGCGGGAGCCGCCTCGGTG
GGCATGCACCTGCTGTCCCCGCCCAGCCGGGGCCTGTTCCACAGGGCCGTGCTGCAGAGC
GGTGCCCCCAATGGACCCTGGGCCACGGTGGGCATGGGAGAGGCCCGTCGCAGGGCCACG
CAGCTGGCCCACCTTGTGGGCTGTCCTCCAGGCGGCACTGGTGGGAATGACACAGAGCTG
GTAGCCTGCCTTCGGACACGACCAGCGCAGGTCCTGGTGAACCACGAATGGCACGTGCTG
CCTCAAGAAAGCGTCTTCCGGTTCTCCTTCGTGCCTGTGGTAGATGGAGACTTCCTCAGT
GACACCCCAGAGGCCCTCATCAACGCGGGAGACTTCCACGGCCTGCAGGTGCTGGTGGGT
GTGGTGAAGGATGAGGGCTCGTATTTTCTGGTTTACGGGGCCCCAGGCTTCAGCAAAGAC
AACGAGTCTCTCATCAGCCGGGCCGAGTTCCTGGCCGGGGTGCGGGTCGGGGTTCCCCAG
GTAAGTGACCTGGCAGCCGAGGCTGTGGTCCTGCATTACACAGACTGGCTGCATCCCGAG
GACCCGGCACGCCTGAGGGAGGCCCTGAGCGATGTGGTGGGCGACCACAATGTCGTGTGC
CCCGTGGCCCAGCTGGCTGGGCGACTGGCTGCCCAGGGTGCCCGGGTCTACGCCTACGTC
TTTGAACACCGTGCTTCCACGCTCTCCTGGCCCCTGTGGATGGGGGTGCCCCACGGCTAC
GAGATCGAGTTCATCTTTGGGATCCCCCTGGACCCCTCTCGAAACTACACGGCAGAGGAG
AAAATCTTCGCCCAGCGACTGATGCGATACTGGGCCAACTTTGCCCGCACAGGGGATCCC
AATGAGCCCCGAGACCCCAAGGCCCCACAATGGCCCCCGTACACGGCGGGGGCTCAGCAG
TACGTTAGTCTGGACCTGCGGCCGCTGGAGGTGCGGCGGGGGCTGCGCGCCCAGGCCTGC
GCCTTCTGGAACCGCTTCCTCCCCAAATTGCTCAGCGCCACCGACACGCTCGACGAGGCG
GAGCGCCAGTGGAAGGCCGAGTTCCACCGCTGGAGCTCCTACATGGTGCACTGGAAGAAC
CAGTTCGACCACTACAGCAAGCAGGATCGCTGCTCAGACCTGTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID ACHE Link Image
Target 1 GenAtlas ID ACHE Link Image
Target 1 HGNC ID HGNC:108 Link Image
Target 1 Chromosome Location 7
Target 1 Locus 7q22
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Kryger G, Harel M, Giles K, Toker L, Velan B, Lazar A, Kronman C, Barak D, Ariel N, Shafferman A, Silman I, Sussman JL: Structures of recombinant native and E202Q mutant human acetylcholinesterase complexed with the snake-venom toxin fasciculin-II. Acta Crystallogr D Biol Crystallogr. 2000 Nov;56(Pt 11):1385-94. [PubMed Link Image]
  2. Wilson MD, Riemer C, Martindale DW, Schnupf P, Boright AP, Cheung TL, Hardy DM, Schwartz S, Scherer SW, Tsui LC, Miller W, Koop BF: Comparative analysis of the gene-dense ACHE/TFR2 region on human chromosome 7q22 with the orthologous region on mouse chromosome 5. Nucleic Acids Res. 2001 Mar 15;29(6):1352-65. [PubMed Link Image]
  3. Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK: The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64. [PubMed Link Image]
  4. Shafferman A, Kronman C, Flashner Y, Leitner M, Grosfeld H, Ordentlich A, Gozes Y, Cohen S, Ariel N, Barak D, et al.: Mutagenesis of human acetylcholinesterase. Identification of residues involved in catalytic activity and in polypeptide folding. J Biol Chem. 1992 Sep 5;267(25):17640-8. [PubMed Link Image]
  5. Velan B, Grosfeld H, Kronman C, Leitner M, Gozes Y, Lazar A, Flashner Y, Marcus D, Cohen S, Shafferman A: The effect of elimination of intersubunit disulfide bonds on the activity, assembly, and secretion of recombinant human acetylcholinesterase. Expression of acetylcholinesterase Cys-580----Ala mutant. J Biol Chem. 1991 Dec 15;266(35):23977-84. [PubMed Link Image]
  6. Soreq H, Ben-Aziz R, Prody CA, Seidman S, Gnatt A, Neville L, Lieman-Hurwitz J, Lev-Lehman E, Ginzberg D, Lipidot-Lifson Y, et al.: Molecular cloning and construction of the coding region for human acetylcholinesterase reveals a G + C-rich attenuating structure. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9688-92. [PubMed Link Image]
  7. Chhajlani V, Derr D, Earles B, Schmell E, August T: Purification and partial amino acid sequence analysis of human erythrocyte acetylcholinesterase. FEBS Lett. 1989 Apr 24;247(2):279-82. [PubMed Link Image]
  8. Karpel R, Ben Aziz-Aloya R, Sternfeld M, Ehrlich G, Ginzberg D, Tarroni P, Clementi F, Zakut H, Soreq H: Expression of three alternative acetylcholinesterase messenger RNAs in human tumor cell lines of different tissue origins. Exp Cell Res. 1994 Feb;210(2):268-77. [PubMed Link Image]
  9. Bartels CF, Zelinski T, Lockridge O: Mutation at codon 322 in the human acetylcholinesterase (ACHE) gene accounts for YT blood group polymorphism. Am J Hum Genet. 1993 May;52(5):928-36. [PubMed Link Image]
  10. Felder CE, Botti SA, Lifson S, Silman I, Sussman JL: External and internal electrostatic potentials of cholinesterase models. J Mol Graph Model. 1997 Oct;15(5):318-27, 335-7. [PubMed Link Image]
Target 1 Drug References
  1. Drake-Baumann R, Seil FJ: Effects of exposure to low-dose pyridostigmine on neuromuscular junctions in vitro. Muscle Nerve. 1999 Jun;22(6):696-703. [PubMed Link Image]
  2. Ricordel I, Meunier J: [Chemical weapons: antidotes. View about the real means, perspectives] Ann Pharm Fr. 2000 Jan;58(1):5-12. [PubMed Link Image]
  3. Prasad V, Scotch R, Chaudhuri AR, Walss C, Fathy DB, Miller C, Luduena RF: Interactions of bovine brain tubulin with pyridostigmine bromide and N,N'-diethyl-m-toluamide. Neurochem Res. 2000 Jan;25(1):19-25. [PubMed Link Image]
  4. Sinton CM, Fitch TE, Petty F, Haley RW: Stressful manipulations that elevate corticosterone reduce blood-brain barrier permeability to pyridostigmine in the Rat. Toxicol Appl Pharmacol. 2000 May 15;165(1):99-105. [PubMed Link Image]
  5. Servatius RJ, Ottenweller JE, Guo W, Beldowicz D, Zhu G, Natelson BH: Effects of inescapable stress and treatment with pyridostigmine bromide on plasma butyrylcholinesterase and the acoustic startle response in rats. Physiol Behav. 2000 May;69(3):239-46. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.