Gallamine Triethiodide

Identification

Name
Gallamine Triethiodide
Accession Number
DB00483  (APRD00712)
Type
Small Molecule
Groups
Approved
Description

A synthetic nondepolarizing blocking drug. The actions of gallamine triethiodide are similar to those of tubocurarine, but this agent blocks the cardiac vagus and may cause sinus tachycardia and, occasionally, hypertension and increased cardiac output. It should be used cautiously in patients at risk from increased heart rate but may be preferred for patients with bradycardia. (From AMA Drug Evaluations Annual, 1992, p198)

Structure
Thumb
Synonyms
  • Gallamin triethiodid
  • Gallamini Triethiodidum
  • Triéthiodure de Gallamine
  • Trietioduro de galamina
External IDs
F 2559 / HL 8583 / RP 3697
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Flaxedil Inj 20mg/mlLiquid20 mgIntravenousAventis Pharma Ltd.1951-12-312003-07-22Canada
International/Other Brands
Flaxedil (Sanofi-Aventis) / Myraxan (Yoo Young) / Sincurarina (Carlo Erba) / Tricuran
Categories
UNII
Q3254X40X2
CAS number
65-29-2
Weight
Average: 891.5291
Monoisotopic: 891.176873061
Chemical Formula
C30H60I3N3O3
InChI Key
REEUVFCVXKWOFE-UHFFFAOYSA-K
InChI
InChI=1S/C30H60N3O3.3HI/c1-10-31(11-2,12-3)22-25-34-28-20-19-21-29(35-26-23-32(13-4,14-5)15-6)30(28)36-27-24-33(16-7,17-8)18-9;;;/h19-21H,10-18,22-27H2,1-9H3;3*1H/q+3;;;/p-3
IUPAC Name
(2-{2,3-bis[2-(triethylazaniumyl)ethoxy]phenoxy}ethyl)triethylazanium triiodide
SMILES
[I-].[I-].[I-].CC[N+](CC)(CC)CCOC1=CC=CC(OCC[N+](CC)(CC)CC)=C1OCC[N+](CC)(CC)CC

Pharmacology

Indication

For use as adjuncts to anesthesia to induce skeletal muscle relaxation and to facilitate the management of patients undergoing mechanical ventilation

Pharmacodynamics

Gallamine Triethiodide is a nondepolarizing neuromuscular blocking drug (NDMRD) used as an adjunct to anesthesia to induce skeletal muscle relaxation. The actions of gallamine triethiodide are similar to those of tubocurarine, but this agent blocks the cardiac vagus and may cause sinus tachycardia and, occasionally, hypertension and increased cardiac output. Muscle groups differ in their sensitivity to these types of relaxants with ocular muscles (controlling eyelids) being most sensitive, followed by the muscles of the neck, jaw, limbs and then abdomen. The diaphragm is the least sensitive muscle to NDMRDs. Although the nondepolarizing neuromuscular blocking drugs do not have the same adverse effects as succinylcholine, their onset of action is slower. They also have a longer duration of action, making them more suitable for maintaining neuromuscular relaxation during major surgical procedures.

Mechanism of action

It competes with acetylcholine (ACh) molecules and binds to muscarinic acetylcholine receptors on the post-synaptic membrane of the motor endplate. It acts by combining with the cholinergic receptor sites in muscle and competitively blocking the transmitter action of acetylcholine. It blocks the action of ACh and prevents activation of the muscle contraction process. It can also act on nicotinic presynaptic acetylcholine receptors which inhibits the release of ACh.

TargetActionsOrganism
AMuscarinic acetylcholine receptor M2
antagonist
Human
AAcetylcholinesterase
inhibitor
Human
UNeuronal acetylcholine receptor subunit alpha-2
antagonist
Human
UMuscarinic acetylcholine receptor M1Not AvailableHuman
UMuscarinic acetylcholine receptor M5Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1,10-PhenanthrolineThe therapeutic efficacy of Gallamine Triethiodide can be decreased when used in combination with 1,10-Phenanthroline.
16-BromoepiandrosteroneThe risk or severity of adverse effects can be increased when 16-Bromoepiandrosterone is combined with Gallamine Triethiodide.
19-norandrostenedioneThe risk or severity of adverse effects can be increased when 19-norandrostenedione is combined with Gallamine Triethiodide.
5-androstenedioneThe risk or severity of adverse effects can be increased when 5-androstenedione is combined with Gallamine Triethiodide.
AcebutololGallamine Triethiodide may increase the bradycardic activities of Acebutolol.
AcetylcholineThe risk or severity of adverse effects can be increased when Gallamine Triethiodide is combined with Acetylcholine.
AcetyldigitoxinGallamine Triethiodide may increase the arrhythmogenic activities of Acetyldigitoxin.
AcetyldigoxinGallamine Triethiodide may increase the arrhythmogenic activities of Acetyldigoxin.
AclidiniumGallamine Triethiodide may increase the anticholinergic activities of Aclidinium.
AgmatineThe therapeutic efficacy of Agmatine can be decreased when used in combination with Gallamine Triethiodide.
Food Interactions
Not Available

References

Synthesis Reference

Fourneau, E.; U.S.Patent 2,544,076; March 6, 1951; assigned to Societe des Usines Chimiques Rhone-Poulenc, France.

General References
Not Available
External Links
Human Metabolome Database
HMDB0014626
PubChem Compound
6172
PubChem Substance
46508651
ChemSpider
5937
ChEMBL
CHEMBL1200993
Therapeutic Targets Database
DAP001127
PharmGKB
PA164745088
MSDS
Download (28.5 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Davis and geck div american cyanamid co
Packagers
Not Available
Dosage forms
FormRouteStrength
LiquidIntravenous20 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)152-153Fourneau, E.; U.S.Patent 2,544,076; March 6, 1951; assigned to Societe des Usines Chimiques Rhone-Poulenc, France.
water solubilitySolubleNot Available
logP3.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility4.65e-06 mg/mLALOGPS
logP-0.38ALOGPS
logP-7.7ChemAxon
logS-8.3ALOGPS
pKa (Strongest Basic)-4.5ChemAxon
Physiological Charge3ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area27.69 Å2ChemAxon
Rotatable Bond Count21ChemAxon
Refractivity189.98 m3·mol-1ChemAxon
Polarizability63.43 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8901
Blood Brain Barrier+0.8616
Caco-2 permeable+0.6256
P-glycoprotein substrateSubstrate0.6912
P-glycoprotein inhibitor INon-inhibitor0.8173
P-glycoprotein inhibitor IINon-inhibitor0.8176
Renal organic cation transporterNon-inhibitor0.6818
CYP450 2C9 substrateNon-substrate0.8147
CYP450 2D6 substrateNon-substrate0.6511
CYP450 3A4 substrateSubstrate0.5708
CYP450 1A2 substrateNon-inhibitor0.8002
CYP450 2C9 inhibitorNon-inhibitor0.8613
CYP450 2D6 inhibitorNon-inhibitor0.8874
CYP450 2C19 inhibitorNon-inhibitor0.8815
CYP450 3A4 inhibitorNon-inhibitor0.9296
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6622
Ames testNon AMES toxic0.6156
CarcinogenicityNon-carcinogens0.5724
BiodegradationNot ready biodegradable0.9841
Rat acute toxicity2.8202 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7691
hERG inhibition (predictor II)Inhibitor0.666
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Phenol ethers
Sub Class
Not Available
Direct Parent
Phenol ethers
Alternative Parents
Phenoxy compounds / Alkyl aryl ethers / Tetraalkylammonium salts / Organopnictogen compounds / Organic iodide salts / Hydrocarbon derivatives / Amines
Substituents
Phenoxy compound / Phenol ether / Alkyl aryl ether / Monocyclic benzene moiety / Quaternary ammonium salt / Tetraalkylammonium salt / Ether / Organic iodide salt / Organic salt / Organic nitrogen compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
G-protein coupled acetylcholine receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM2
Uniprot ID
P08172
Uniprot Name
Muscarinic acetylcholine receptor M2
Molecular Weight
51714.605 Da
References
  1. Huang XP, Prilla S, Mohr K, Ellis J: Critical amino acid residues of the common allosteric site on the M2 muscarinic acetylcholine receptor: more similarities than differences between the structurally divergent agents gallamine and bis(ammonio)alkane-type hexamethylene-bis-[dimethyl-(3-phthalimidopropyl)ammonium]dibromide. Mol Pharmacol. 2005 Sep;68(3):769-78. Epub 2005 Jun 3. [PubMed:15937215]
  2. De Vries B, Roffel AF, Kooistra JM, Meurs H, Zaagsma J: Effects of fenoterol on beta-adrenoceptor and muscarinic M2 receptor function in bovine tracheal smooth muscle. Eur J Pharmacol. 2001 May 11;419(2-3):253-9. [PubMed:11426849]
  3. Cembala TM, Forde SC, Appadu BL, Lambert DG: Allosteric interaction of the neuromuscular blockers vecuronium and pancuronium with recombinant human muscarinic M2 receptors. Eur J Pharmacol. 2007 Aug 13;569(1-2):37-40. Epub 2007 May 22. [PubMed:17588565]
  4. Ten Berge RE, Krikke M, Teisman AC, Roffel AF, Zaagsma J: Dysfunctional muscarinic M2 autoreceptors in vagally induced bronchoconstriction of conscious guinea pigs after the early allergic reaction. Eur J Pharmacol. 1996 Dec 27;318(1):131-9. [PubMed:9007524]
  5. Spina D, Minshall E, Goldie RG, Page CP: The effect of allosteric antagonists in modulating muscarinic M2-receptor function in guinea-pig isolated trachea. Br J Pharmacol. 1994 Jul;112(3):901-5. [PubMed:7522861]
  6. Redka DS, Pisterzi LF, Wells JW: Binding of orthosteric ligands to the allosteric site of the M(2) muscarinic cholinergic receptor. Mol Pharmacol. 2008 Sep;74(3):834-43. doi: 10.1124/mol.108.048074. Epub 2008 Jun 13. [PubMed:18552124]
  7. Maier-Peuschel M, Frolich N, Dees C, Hommers LG, Hoffmann C, Nikolaev VO, Lohse MJ: A fluorescence resonance energy transfer-based M2 muscarinic receptor sensor reveals rapid kinetics of allosteric modulation. J Biol Chem. 2010 Mar 19;285(12):8793-800. doi: 10.1074/jbc.M109.098517. Epub 2010 Jan 18. [PubMed:20083608]
  8. Ehlert FJ, Griffin MT: Two-state models and the analysis of the allosteric effect of gallamine at the M2 muscarinic receptor. J Pharmacol Exp Ther. 2008 Jun;325(3):1039-60. doi: 10.1124/jpet.108.136960. Epub 2008 Feb 27. [PubMed:18305010]
  9. Elsinghorst PW, Cieslik JS, Mohr K, Trankle C, Gutschow M: First gallamine-tacrine hybrid: design and characterization at cholinesterases and the M2 muscarinic receptor. J Med Chem. 2007 Nov 15;50(23):5685-95. Epub 2007 Oct 18. [PubMed:17944454]
  10. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine hydrolase activity
Specific Function
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name
ACHE
Uniprot ID
P22303
Uniprot Name
Acetylcholinesterase
Molecular Weight
67795.525 Da
References
  1. Radic Z, Taylor P: The influence of peripheral site ligands on the reaction of symmetric and chiral organophosphates with wildtype and mutant acetylcholinesterases. Chem Biol Interact. 1999 May 14;119-120:111-7. [PubMed:10421444]
  2. Radic Z, Taylor P: Peripheral site ligands accelerate inhibition of acetylcholinesterase by neutral organophosphates. J Appl Toxicol. 2001 Dec;21 Suppl 1:S13-4. [PubMed:11920914]
  3. Robaire B, Kato G: Effects of edrophonium, eserine, decamethonium, d-tubocurarine, and gallamine on the kinetics of membrane-bound and solubilized eel acetylcholinesterase. Mol Pharmacol. 1975 Nov;11(6):722-34. [PubMed:1207670]
  4. Seto Y, Shinohara T: Structure-activity relationship of reversible cholinesterase inhibitors including paraquat. Arch Toxicol. 1988 Aug;62(1):37-40. [PubMed:3190453]
  5. Bourgeois JP, Betz H, Changuex JP: [Effects of chronic paralysis of chick embryo by flaxedil on the development of the neuromuscular junction]. C R Acad Sci Hebd Seances Acad Sci D. 1978 Mar 13;286(10):773-6. [PubMed:417864]
  6. Elsinghorst PW, Cieslik JS, Mohr K, Trankle C, Gutschow M: First gallamine-tacrine hybrid: design and characterization at cholinesterases and the M2 muscarinic receptor. J Med Chem. 2007 Nov 15;50(23):5685-95. Epub 2007 Oct 18. [PubMed:17944454]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Drug binding
Specific Function
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
Gene Name
CHRNA2
Uniprot ID
Q15822
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-2
Molecular Weight
59764.82 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Aoshima H, Inoue Y, Hori K: Inhibition of ionotropic neurotransmitter receptors by antagonists: strategy to estimate the association and the dissociation rate constant of antagonists with very strong affinity to the receptors. J Biochem. 1992 Oct;112(4):495-502. [PubMed:1337082]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 Da
References
  1. Lazareno S, Popham A, Birdsall NJ: Allosteric interactions of staurosporine and other indolocarbazoles with N-[methyl-(3)H]scopolamine and acetylcholine at muscarinic receptor subtypes: identification of a second allosteric site. Mol Pharmacol. 2000 Jul;58(1):194-207. [PubMed:10860942]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM5
Uniprot ID
P08912
Uniprot Name
Muscarinic acetylcholine receptor M5
Molecular Weight
60073.205 Da
References
  1. Prilla S, Schrobang J, Ellis J, Holtje HD, Mohr K: Allosteric interactions with muscarinic acetylcholine receptors: complex role of the conserved tryptophan M2422Trp in a critical cluster of amino acids for baseline affinity, subtype selectivity, and cooperativity. Mol Pharmacol. 2006 Jul;70(1):181-93. Epub 2006 Apr 26. [PubMed:16641315]

Drug created on June 13, 2005 07:24 / Updated on August 02, 2018 04:22