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Identification
NameTrimethaphan
Accession NumberDB01116  (APRD00044)
TypeSmall Molecule
GroupsApproved
Description

A nicotinic antagonist that has been used as a ganglionic blocker in hypertension, as an adjunct to anesthesia, and to induce hypotension during surgery. [PubChem]

Structure
Thumb
Synonyms
Thimethaphan
Trimetaphan
Trimetaphanum
Trimethaphan
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
ArfonadNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Trimethaphan camsylate
ThumbNot applicableDBSALT001381
Categories
UNII6G8X656T45
CAS number7187-66-8
WeightAverage: 365.512
Monoisotopic: 365.168759122
Chemical FormulaC22H25N2OS
InChI KeyInChIKey=CHQOEHPMXSHGCL-UHFFFAOYSA-N
InChI
InChI=1S/C22H25N2OS/c25-22-23(14-17-8-3-1-4-9-17)19-16-26-13-7-12-20(26)21(19)24(22)15-18-10-5-2-6-11-18/h1-6,8-11,19-21H,7,12-16H2/q+1
IUPAC Name
3,5-dibenzyl-4-oxo-8λ⁴-thia-3,5-diazatricyclo[6.3.0.0²,⁶]undecan-8-ylium
SMILES
O=C1N(CC2=CC=CC=C2)C2C[S+]3CCCC3C2N1CC1=CC=CC=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as thienoimidazolidines. These are heterocyclic compounds containing a thiophene ring fused to an imidazolidine ring. Thiophene is 5-membered ring consisting of four carbon atoms and one sulfur atom. Imidazolidine is 5-membered saturated ring of three carbon atoms, and two nitrogen centers at the 1- and 3-positions.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassThienoimidazolidines
Sub ClassNot Available
Direct ParentThienoimidazolidines
Alternative Parents
Substituents
  • Thienoimidazolidine
  • Phenylmethylamine
  • Benzylamine
  • Benzenoid
  • Imidazolidinone
  • Monocyclic benzene moiety
  • Thiophene
  • Imidazolidine
  • Urea
  • Tertiary amine
  • Azacycle
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Organic cation
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the controlled reduction of blood pressure during surgery and in the treatment of hypertensive emergencies.
PharmacodynamicsTrimethaphan is indicated for production of controlled hypotension during surgery to reduce bleeding into the surgical field and also for rapid reduction of blood pressure in the treatment of hypertensive emergencies, especially in patients with acute dissecting aneurysm, and in the emergency treatment of pulmonary edema in patients with pulmonary hypertension associated with systemic hypertension.
Mechanism of actionTrimethaphan is a ganglionic blocking agent prevents stimulation of postsynaptic receptors by competing with acetylcholine for these receptor sites. Additional effects may include direct peripheral vasodilation and release of histamine. Trimethaphan's hypotensive effect is due to reduction in sympathetic tone and vasodilation, and is primarily postural.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9641
Blood Brain Barrier+0.9897
Caco-2 permeable-0.5053
P-glycoprotein substrateSubstrate0.6942
P-glycoprotein inhibitor IInhibitor0.6012
P-glycoprotein inhibitor IINon-inhibitor0.6356
Renal organic cation transporterInhibitor0.6812
CYP450 2C9 substrateNon-substrate0.7161
CYP450 2D6 substrateNon-substrate0.6162
CYP450 3A4 substrateNon-substrate0.5152
CYP450 1A2 substrateNon-inhibitor0.5223
CYP450 2C9 inhibitorInhibitor0.5
CYP450 2D6 inhibitorInhibitor0.5134
CYP450 2C19 inhibitorInhibitor0.7361
CYP450 3A4 inhibitorNon-inhibitor0.8947
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.847
Ames testNon AMES toxic0.6511
CarcinogenicityNon-carcinogens0.9545
BiodegradationNot ready biodegradable0.9606
Rat acute toxicity2.3658 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.597
hERG inhibition (predictor II)Inhibitor0.7575
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP3.473Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00665 mg/mLALOGPS
logP4.4ALOGPS
logP2.32ChemAxon
logS-4.8ALOGPS
pKa (Strongest Basic)-2ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area23.55 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity105.43 m3·mol-1ChemAxon
Polarizability40.13 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesC02BA01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Receptor binding
Specific Function:
Ionotropic receptor with a probable role in the modulation of auditory stimuli. Agonist binding may induce an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The channel is permeable to a range of divalent cations including calcium, the influx of which may activate a potassium current which hyperpolarizes t...
Gene Name:
CHRNA10
Uniprot ID:
Q9GZZ6
Molecular Weight:
49704.295 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. Kurenny DE, Selyanko AA, Derkach VA, Gmiro VE, Skok VI: Mechanism of long-lasting block of ganglion nicotinic receptors by mono-ammonium compounds with long aliphatic chain. J Auton Nerv Syst. 1994 Aug;48(3):231-40. [PubMed:7963258 ]
  4. Loiacono R, Stephenson J, Stevenson J, Mitchelson F: Multiple binding sites for nicotine receptor antagonists in inhibiting [3H](-)-nicotine binding in rat cortex. Neuropharmacology. 1993 Sep;32(9):847-53. [PubMed:8232788 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Identical protein binding
Specific Function:
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name:
BCHE
Uniprot ID:
P06276
Molecular Weight:
68417.575 Da
References
  1. Nakamura K, Koide M, Imanaga T, Ogasawara H, Takahashi M, Yoshikawa M: Prolonged neuromuscular blockade following trimetaphan infusion. A case report and in vitro study of cholinesterase inhibition. Anaesthesia. 1980 Dec;35(12):1202-7. [PubMed:7457791 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23