Tetrodotoxin
Identification
- Generic Name
- Tetrodotoxin
- DrugBank Accession Number
- DB05232
- Background
An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order tetraodontiformes, which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction. Tetrodotoxin is being investigated by Wex Pharmaceuticals for the treatment of chronic and breakthrough pain in advanced cancer patients as well as for the treatment of opioid dependence.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Tetrodotoxin (DB05232)
- Weight
- Average: 319.268
Monoisotopic: 319.101564535 - Chemical Formula
- C11H17N3O8
- Synonyms
- Tetrodotoxin
Pharmacology
- Indication
For the treatment of chronic and breakthrough pain in advanced cancer patients as well as for the treatment of opioid dependence.
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Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Not Available
- Mechanism of action
Tetrodotoxin binds to site 1 of the fast voltage-gated sodium channel located at the extracellular pore opening. The binding of any molecules to this site will temporarily disable the function of the ion channel. Saxitoxin and several of the conotoxins also bind the same site.
Target Actions Organism USodium channel protein type 1 subunit alpha Not Available Humans USodium channel protein type 2 subunit alpha Not Available Humans USodium channel protein type 3 subunit alpha Not Available Humans USodium channel protein type 8 subunit alpha Not Available Humans - 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.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Death has occurred within 17 minutes of ingestion.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- 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 software1,2-Benzodiazepine The risk or severity of adverse effects can be increased when Tetrodotoxin is combined with 1,2-Benzodiazepine. Acetazolamide The risk or severity of adverse effects can be increased when Acetazolamide is combined with Tetrodotoxin. Acetophenazine The risk or severity of adverse effects can be increased when Acetophenazine is combined with Tetrodotoxin. Aclidinium Tetrodotoxin may increase the central nervous system depressant (CNS depressant) activities of Aclidinium. Agomelatine The risk or severity of adverse effects can be increased when Tetrodotoxin is combined with Agomelatine. Alfentanil The risk or severity of adverse effects can be increased when Alfentanil is combined with Tetrodotoxin. Alimemazine The risk or severity of adverse effects can be increased when Alimemazine is combined with Tetrodotoxin. Almotriptan The risk or severity of adverse effects can be increased when Almotriptan is combined with Tetrodotoxin. Alosetron The risk or severity of adverse effects can be increased when Alosetron is combined with Tetrodotoxin. Alprazolam The risk or severity of adverse effects can be increased when Alprazolam is combined with Tetrodotoxin. 
Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - 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.- International/Other Brands
- Tectin / Tetrodin
Categories
- Drug Categories
- Anesthetics
- Anesthetics, Local
- Biological Factors
- Cardiovascular Agents
- Central Nervous System Agents
- Central Nervous System Depressants
- Compounds used in a research, industrial, or household setting
- Heterocyclic Compounds, Fused-Ring
- Marine Toxins
- Membrane Transport Modulators
- Noxae
- Peripheral Nervous System Agents
- Poisons
- Quinazolines
- Sensory System Agents
- Sodium Channel Blockers
- Toxic Actions
- Toxins, Biological
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as tetrodotoxins. These are compounds structurally characterized by the presence of the tetrodotoxin skeleton, which is based on 5,7-(epoxymethanooxy)quinazolin-10-olate moiety.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Diazanaphthalenes
- Sub Class
- Benzodiazines
- Direct Parent
- Tetrodotoxins
- Alternative Parents
- 1,3-dioxanes / Hydropyrimidines / Monosaccharides / Oxanes / Tertiary alcohols / Secondary alcohols / Cyclic alcohols and derivatives / Guanidines / Orthocarboxylic acid derivatives / Propargyl-type 1,3-dipolar organic compounds show 11 more
- Substituents
- 1,4,5,6-tetrahydropyrimidine / Alcohol / Aliphatic heteropolycyclic compound / Alkanolamine / Alkoxide / Azacycle / Carboximidamide / Cyclic alcohol / Guanidine / Hydrocarbon derivative show 20 more
- Molecular Framework
- Aliphatic heteropolycyclic compounds
- External Descriptors
- Alkaloids, Tetrodotoxins (C11692)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 3KUM2721U9
- CAS number
- 4368-28-9
- InChI Key
- SLBCPBUVHCASIJ-UFHSVNPDSA-O
- InChI
- InChI=1S/C11H16N3O8/c12-8-13-6(17)2-4-9(19,1-15)5-3(16)10(2,14-8)7(18)11(20,21-4)22-5/h2-7,15-19H,1H2,(H3,12,13,14)/q-1/p+1/t2?,3?,4?,5-,6?,7-,9?,10?,11?/m0/s1
- IUPAC Name
- (11S,13S)-3-amino-5,12,13,14-tetrahydroxy-14-(hydroxymethyl)-8,10-dioxa-2,4-diazatetracyclo[7.3.1.1⁷,¹¹.0¹,⁶]tetradec-3-en-4-ium-9-olate
- SMILES
- [H][C@]12OC3([O-])OC(C4C(O)[NH+]=C(N)NC4(C1O)[C@@H]3O)C2(O)CO
References
- General References
- Not Available
- External Links
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Completed Treatment Malignancies / Pain 2 2 Terminated Treatment Neuropathic Pain / Pain / Peripheral neuropathy 1 1 Completed Basic Science TQT Study 1 1 Completed Screening Healthy Subjects (HS) 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 pKa 8.76 MERCK INDEX (1996) - Predicted Properties
Property Value Source Water Solubility 117.0 mg/mL ALOGPS logP 0.42 ALOGPS logP -4.8 ChemAxon logS -0.5 ALOGPS pKa (Strongest Acidic) 10.4 ChemAxon pKa (Strongest Basic) 9.62 ChemAxon Physiological Charge 1 ChemAxon Hydrogen Acceptor Count 10 ChemAxon Hydrogen Donor Count 8 ChemAxon Polar Surface Area 194.69 Å2 ChemAxon Rotatable Bond Count 1 ChemAxon Refractivity 86.74 m3·mol-1 ChemAxon Polarizability 27.83 Å3 ChemAxon Number of Rings 4 ChemAxon Bioavailability 1 ChemAxon Rule of Five No ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption - 0.9781 Blood Brain Barrier - 0.6809 Caco-2 permeable - 0.6763 P-glycoprotein substrate Substrate 0.5082 P-glycoprotein inhibitor I Non-inhibitor 0.9376 P-glycoprotein inhibitor II Non-inhibitor 0.988 Renal organic cation transporter Non-inhibitor 0.9066 CYP450 2C9 substrate Non-substrate 0.7925 CYP450 2D6 substrate Non-substrate 0.7989 CYP450 3A4 substrate Non-substrate 0.5602 CYP450 1A2 substrate Non-inhibitor 0.8008 CYP450 2C9 inhibitor Non-inhibitor 0.884 CYP450 2D6 inhibitor Non-inhibitor 0.908 CYP450 2C19 inhibitor Non-inhibitor 0.8374 CYP450 3A4 inhibitor Non-inhibitor 0.9834 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9821 Ames test Non AMES toxic 0.5547 Carcinogenicity Non-carcinogens 0.9196 Biodegradation Not ready biodegradable 0.9587 Rat acute toxicity 2.5238 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9949 hERG inhibition (predictor II) Non-inhibitor 0.8694
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key 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 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Voltage-gated sodium channel activity
- Specific Function
- Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a...
- Gene Name
- SCN1A
- Uniprot ID
- P35498
- Uniprot Name
- Sodium channel protein type 1 subunit alpha
- Molecular Weight
- 228969.49 Da
References
- Sage D, Salin P, Alcaraz G, Castets F, Giraud P, Crest M, Mazet B, Clerc N: Na(v)1.7 and Na(v)1.3 are the only tetrodotoxin-sensitive sodium channels expressed by the adult guinea pig enteric nervous system. J Comp Neurol. 2007 Oct 1;504(4):363-78. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Voltage-gated sodium channel activity
- Specific Function
- Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a...
- Gene Name
- SCN2A
- Uniprot ID
- Q99250
- Uniprot Name
- Sodium channel protein type 2 subunit alpha
- Molecular Weight
- 227972.64 Da
References
- Sage D, Salin P, Alcaraz G, Castets F, Giraud P, Crest M, Mazet B, Clerc N: Na(v)1.7 and Na(v)1.3 are the only tetrodotoxin-sensitive sodium channels expressed by the adult guinea pig enteric nervous system. J Comp Neurol. 2007 Oct 1;504(4):363-78. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Voltage-gated sodium channel activity
- Specific Function
- Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a...
- Gene Name
- SCN3A
- Uniprot ID
- Q9NY46
- Uniprot Name
- Sodium channel protein type 3 subunit alpha
- Molecular Weight
- 226291.905 Da
References
- Sage D, Salin P, Alcaraz G, Castets F, Giraud P, Crest M, Mazet B, Clerc N: Na(v)1.7 and Na(v)1.3 are the only tetrodotoxin-sensitive sodium channels expressed by the adult guinea pig enteric nervous system. J Comp Neurol. 2007 Oct 1;504(4):363-78. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Voltage-gated sodium channel activity
- Specific Function
- Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a...
- Gene Name
- SCN8A
- Uniprot ID
- Q9UQD0
- Uniprot Name
- Sodium channel protein type 8 subunit alpha
- Molecular Weight
- 225278.005 Da
References
- Sage D, Salin P, Alcaraz G, Castets F, Giraud P, Crest M, Mazet B, Clerc N: Na(v)1.7 and Na(v)1.3 are the only tetrodotoxin-sensitive sodium channels expressed by the adult guinea pig enteric nervous system. J Comp Neurol. 2007 Oct 1;504(4):363-78. [Article]
Drug created on October 21, 2007 22:24 / Updated on February 21, 2021 18:51