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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
SynonymLanguageCode
ThimethaphanNot AvailableNot Available
TrimetaphanNot AvailableNot Available
TrimetaphanumNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
ArfonadNot Available
Brand mixturesNot Available
Categories
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-8$l^{4}-thia-3,5-diazatricyclo[6.3.0.0^{2,6}]undecan-8-ylium
SMILES
O=C1N(CC2=CC=CC=C2)C2C[S+]3CCCC3C2N1CC1=CC=CC=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassThienoimidazolidines
SubclassNot Available
Direct parentThienoimidazolidines
Alternative parentsBenzene and Substituted Derivatives; Imidazolidinones; Thiophenes; Tertiary Amines; Polyamines
Substituentsbenzene; imidazolidinone; imidazolidine; thiophene; tertiary amine; polyamine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the thienoimidazolidines. These are heterocyclic compounds containing a thiophene ring fused to an imidazolidine ring.
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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
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
Property Value Probability
Human Intestinal Absorption + 0.9641
Blood Brain Barrier + 0.9897
Caco-2 permeable - 0.5053
P-glycoprotein substrate Substrate 0.6942
P-glycoprotein inhibitor I Inhibitor 0.6012
P-glycoprotein inhibitor II Non-inhibitor 0.6356
Renal organic cation transporter Inhibitor 0.6812
CYP450 2C9 substrate Non-substrate 0.7161
CYP450 2D6 substrate Non-substrate 0.6162
CYP450 3A4 substrate Non-substrate 0.5152
CYP450 1A2 substrate Non-inhibitor 0.5223
CYP450 2C9 substrate Inhibitor 0.5
CYP450 2D6 substrate Inhibitor 0.5134
CYP450 2C19 substrate Inhibitor 0.7361
CYP450 3A4 substrate Non-inhibitor 0.8947
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.847
Ames test Non AMES toxic 0.6511
Carcinogenicity Non-carcinogens 0.9545
Biodegradation Not ready biodegradable 0.9606
Rat acute toxicity 2.3658 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Strong inhibitor 0.597
hERG inhibition (predictor II) Inhibitor 0.7575
Pharmacoeconomics
Manufacturers
  • Hoffmann la roche inc
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
logP3.473Not Available
Predicted Properties
PropertyValueSource
water solubility6.65e-03 g/lALOGPS
logP4.4ALOGPS
logP2.32ChemAxon
logS-4.8ALOGPS
pKa (strongest basic)-2ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count1ChemAxon
hydrogen donor count0ChemAxon
polar surface area23.55ChemAxon
rotatable bond count4ChemAxon
refractivity105.43ChemAxon
polarizability40.13ChemAxon
number of rings5ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC07174
PubChem Compound23576
PubChem Substance46508994
ChemSpider22044
ChEBI9728
ChEMBL
Therapeutic Targets DatabaseDAP001143
PharmGKBPA451784
WikipediaTrimethaphan
ATC CodesC02BA01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

1. Neuronal acetylcholine receptor subunit alpha-10

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Neuronal acetylcholine receptor subunit alpha-10 Q9GZZ6 Details

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
  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
  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
  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

1. Cholinesterase

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Cholinesterase P06276 Details

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

Comments
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13