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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyTrimethaphan
Identification
- Name
- Trimethaphan
- Accession Number
- DB01116 (APRD00044)
- Type
- Small Molecule
- Groups
- Approved, Investigational
- 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.
- Structure
Structure for Trimethaphan (DB01116)
- Synonyms
- Thimethaphan
- Trimetaphan
- Trimetaphanum
- Product Ingredients
Ingredient UNII CAS InChI Key Trimethaphan camsylate 8W556014K9 68-91-7 HALWUDBBYKMYPW-STOWLHSFSA-M - International/Other Brands
- Arfonad
- 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
- UNII
- 6G8X656T45
- CAS number
- 7187-66-8
- Weight
- Average: 365.512
Monoisotopic: 365.168759122 - Chemical Formula
- C22H25N2OS
- 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-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
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Pharmacology
- Indication
For the controlled reduction of blood pressure during surgery and in the treatment of hypertensive emergencies.
- 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
- Toxicity
- Not Available
- Affected organisms
- Humans and other mammals
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
Drug Interaction 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid Trimethaphan may increase the hypotensive activities of 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid. 1-benzylimidazole 1-benzylimidazole may decrease the antihypertensive activities of Trimethaphan. 1,10-Phenanthroline The therapeutic efficacy of Trimethaphan can be decreased when used in combination with 1,10-Phenanthroline. 2,5-Dimethoxy-4-ethylamphetamine 2,5-Dimethoxy-4-ethylamphetamine may decrease the antihypertensive activities of Trimethaphan. 2,5-Dimethoxy-4-ethylthioamphetamine 2,5-Dimethoxy-4-ethylthioamphetamine may decrease the antihypertensive activities of Trimethaphan. 4-Bromo-2,5-dimethoxyamphetamine 4-Bromo-2,5-dimethoxyamphetamine may decrease the antihypertensive activities of Trimethaphan. 4-Methoxyamphetamine 4-Methoxyamphetamine may decrease the antihypertensive activities of Trimethaphan. 5-(2-methylpiperazine-1-sulfonyl)isoquinoline The risk or severity of adverse effects can be increased when 5-(2-methylpiperazine-1-sulfonyl)isoquinoline is combined with Trimethaphan. 5-methoxy-N,N-dimethyltryptamine 5-methoxy-N,N-dimethyltryptamine may decrease the antihypertensive activities of Trimethaphan. 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypotensive activities of Trimethaphan. - Food Interactions
- Not Available
References
- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0015248
- KEGG Compound
- C07174
- PubChem Compound
- 23576
- PubChem Substance
- 46508994
- ChemSpider
- 22044
- BindingDB
- 82545
- ChEBI
- 9728
- ChEMBL
- CHEMBL1201329
- Therapeutic Targets Database
- DAP001143
- PharmGKB
- PA451784
- Wikipedia
- Trimethaphan
- ATC Codes
- C02BA01 — Trimetaphan
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 1 Completed Not Available BMI >30 kg/m2 / High Blood Pressure (Hypertension) 1 1 Completed Diagnostic BMI >30 kg/m2 / High Blood Pressure (Hypertension) / Progressive autonomic failure / Shy-Drager Syndrome 1 1 Completed Other Endothelial Dysfunction 1 1 Recruiting Basic Science Insulin Resistance 1 1 Recruiting Basic Science Idiopathic orthostatic hypotension / Multiple System Atrophy (MSA) / Supine Hypertension 1 1 Recruiting Other High Blood Pressure (Hypertension) 1 1 Recruiting Other High Blood Pressure (Hypertension) / Hypertension,Essential 1 Not Available Completed Not Available BMI >30 kg/m2 1 Not Available Completed Not Available High Blood Pressure (Hypertension) / Progressive autonomic failure 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 Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available
Taxonomy
- 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
- Thienoimidazolidine / Monocyclic benzene moiety / Imidazolidinone / Benzenoid / Imidazolidine / Thiolane / Thiophene / Carbonic acid derivative / Urea / Azacycle show 10 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- sulfonium compound (CHEBI:9728)
Targets
- 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. [PubMed:17139284]
- 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]
- 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]
- 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
- 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. [PubMed:7457791]
Drug created on June 13, 2005 07:24 / Updated on December 16, 2018 06:46