Identification
- Generic Name
- Trimethaphan
- DrugBank Accession Number
- DB01116
- Background
A nicotinic antagonist that has been used as a ganglionic blocker in hypertension, as an adjunct to anesthesia, and to induce hypotension during surgery.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Trimethaphan (DB01116)
- Weight
- Average: 365.512
Monoisotopic: 365.168759122 - Chemical Formula
- C22H25N2OS
- Synonyms
- Thimethaphan
- Trimetaphan
- Trimetaphanum
Pharmacology
- Indication
For the controlled reduction of blood pressure during surgery and in the treatment of hypertensive emergencies.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Trimethaphan 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 action
Trimethaphan 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.
Target Actions Organism ANeuronal acetylcholine receptor subunit alpha-10 antagonistHumans - 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
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbaloparatide Abaloparatide may increase the hypotensive activities of Trimethaphan. Acebutolol Trimethaphan may increase the hypotensive activities of Acebutolol. Aceclofenac The therapeutic efficacy of Trimethaphan can be decreased when used in combination with Aceclofenac. Acemetacin The therapeutic efficacy of Trimethaphan can be decreased when used in combination with Acemetacin. Acetazolamide The risk or severity of adverse effects can be increased when Acetazolamide is combined with Trimethaphan. - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Trimethaphan camsylate 8W556014K9 68-91-7 HALWUDBBYKMYPW-STOWLHSFSA-M - International/Other Brands
- Arfonad
Categories
- ATC Codes
- C02BA01 — Trimetaphan
- Drug Categories
- Adjuvants, Anesthesia
- Antiadrenergic Agents, Ganglion-Blocking
- Anticholinergic Agents
- Antihypertensive Agents
- Autonomic Agents
- Cardiovascular Agents
- Central Nervous System Agents
- Cholinergic Agents
- Cholinesterase substrates
- Ganglion Blockers
- Imidazoles
- Neurotransmitter Agents
- Nicotinic Antagonists
- Peripheral Nervous System Agents
- Sulfonium Derivatives
- Vasodilating Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This 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.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Thienoimidazolidines
- Sub Class
- Not Available
- Direct Parent
- Thienoimidazolidines
- Alternative Parents
- Imidazolidinones / Benzene and substituted derivatives / Thiophenes / Thiolanes / Ureas / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives show 2 more
- Substituents
- Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carbonic acid derivative / Carbonyl group / Hydrocarbon derivative / Imidazolidine / Imidazolidinone / Monocyclic benzene moiety / Organic cation show 10 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- sulfonium compound (CHEBI:9728)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 6G8X656T45
- CAS number
- 7187-66-8
- InChI Key
- 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-8lambda4-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
References
- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0015248
- KEGG Compound
- C07174
- PubChem Compound
- 23576
- PubChem Substance
- 46508994
- ChemSpider
- 22044
- BindingDB
- 82545
- 10828
- ChEBI
- 9728
- ChEMBL
- CHEMBL1201329
- Therapeutic Targets Database
- DAP001143
- PharmGKB
- PA451784
- Wikipedia
- Trimetaphan_camsilate
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 1 Active Not Recruiting Basic Science Multiple System Atrophy (MSA) / Orthostatic Hypotension / Supine Hypertension 1 1 Active Not Recruiting Other Hypertension 1 1 Completed Not Available Chronic Fatigue Syndrome/ Myalgic Encephalitis (CFS/ME) / Orthostatic Intolerance / Postural Orthostatic Tachycardia Syndrome (POTS) 1 1 Completed Not Available Hypertension / Obesity 1 1 Completed Diagnostic Hypertension / Obesity / Progressive autonomic failure / Shy-Drager Syndrome 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source logP 3.473 Not Available - Predicted Properties
Property Value Source Water Solubility 0.00665 mg/mL ALOGPS logP 4.4 ALOGPS logP 2.32 Chemaxon logS -4.8 ALOGPS pKa (Strongest Basic) -2 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 1 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 23.55 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 105.43 m3·mol-1 Chemaxon Polarizability 40.13 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - 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 inhibitor Inhibitor 0.5 CYP450 2D6 inhibitor Inhibitor 0.5134 CYP450 2C19 inhibitor Inhibitor 0.7361 CYP450 3A4 inhibitor 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
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-004l-9271000000-f658de0375569e641f0c Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 195.3599781 predictedDarkChem Lite v0.1.0 [M-H]- 175.25975 predictedDeepCCS 1.0 (2019) [M+H]+ 195.1800781 predictedDarkChem Lite v0.1.0 [M+H]+ 177.61775 predictedDeepCCS 1.0 (2019) [M+Na]+ 195.6907781 predictedDarkChem Lite v0.1.0 [M+Na]+ 184.38396 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- Kind
- Protein
- Organism
- Humans
- 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 i...
- Gene Name
- CHRNA10
- Uniprot ID
- Q9GZZ6
- Uniprot Name
- Neuronal acetylcholine receptor subunit alpha-10
- Molecular Weight
- 49704.295 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- 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
- Uniprot Name
- Cholinesterase
- Molecular Weight
- 68417.575 Da
References
- 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. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 02, 2024 22:54