Bezitramide
Identification
- Generic Name
- Bezitramide
- DrugBank Accession Number
- DB01459
- Background
Bezitramide is a narcotic analgesic which was discovered in 1961, clinically tested around the 1970's 1, and marketed under the name Burgodin. After cases of fatal overdose in the Netherlands in 2004 the drug was withdrawn from the market.
Bezitramide has never been FDA approved and is currently a schedule II drug.
- Type
- Small Molecule
- Groups
- Experimental, Illicit, Withdrawn
- Structure
- Weight
- Average: 492.6114
Monoisotopic: 492.252526288 - Chemical Formula
- C31H32N4O2
- Synonyms
- Bezitramida
- Bezitramide
- Bezitramidum
- External IDs
- IDS-NB-007
- R 4845
- R-4845
Pharmacology
- Indication
A narcotic analgesic once used for the treatment of severe chronic pain. 1
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
Bezitramide acts in the body to relieve pain with a potency 20 times that of methadone 1. Its duration of action is relatively long, lasting up to 12 hours post oral administration, after the achievement of steady state. Its onset of action is slow, with a peak in analgesic effect noted between 2.5-3.5 hours after dosing.
It is noted to illicit a strong antitussive effect, which could be of benefit to patients with bronchial carcinoma.
- Mechanism of action
- Not Available
- Absorption
Bezitramide has poor water solubility, thus administration is restricted to the oral route. 1
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Bezitramide is a prodrug which undergoes rapid hydrolysis of a proprionyl-group to form the major metabolite, R-4618. R-4618 has analgesic properties similar to the parent compound.1 Metabolism occurs in the gastrointestinal tract under both acidic and alkaline conditions 1.
- Route of elimination
Less than 0.3% of the dose was excreted unchanged in the urine. High concentrations in feces suggested incomplete absorption of biliary excretion.
Experiments in rats demonstrated extensive (up to 70%) biliary excretion, and less than 3% urinary excretion. 1
- Half-life
11-24h. 1
- 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
- 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 Bezitramide is combined with 1,2-Benzodiazepine. Acetazolamide The therapeutic efficacy of Acetazolamide can be decreased when used in combination with Bezitramide. Acetophenazine The risk or severity of hypotension and CNS depression can be increased when Acetophenazine is combined with Bezitramide. Aclidinium The risk or severity of adverse effects can be increased when Aclidinium is combined with Bezitramide. Alfentanil The risk or severity of adverse effects can be increased when Alfentanil is combined with Bezitramide. - 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
- Burgodin (Janssen Pharmceutica)
Categories
- ATC Codes
- N02AC05 — Bezitramide
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as diphenylacetonitriles. These are cyclic aromatic compounds containing a diphenylacetonitrile moiety, which consists of a diphenylmethane linked to and acetonitrile to form 2,2-diphenylacetonitrile.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Diphenylacetonitriles
- Direct Parent
- Diphenylacetonitriles
- Alternative Parents
- Diphenylmethanes / Benzimidazoles / N-acylimidazoles / N-acyl ureas / Carbonylimidazoles / Aralkylamines / Piperidines / Heteroaromatic compounds / Trialkylamines / Nitriles show 5 more
- Substituents
- Amine / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Azole / Benzimidazole / Carbonitrile / Diphenylacetonitrile / Diphenylmethane / Heteroaromatic compound show 19 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 3KXW0Y310I
- CAS number
- 15301-48-1
- InChI Key
- FLKWNFFCSSJANB-UHFFFAOYSA-N
- InChI
- InChI=1S/C31H32N4O2/c1-2-29(36)35-28-16-10-9-15-27(28)34(30(35)37)26-17-20-33(21-18-26)22-19-31(23-32,24-11-5-3-6-12-24)25-13-7-4-8-14-25/h3-16,26H,2,17-22H2,1H3
- IUPAC Name
- 4-[4-(2-oxo-3-propanoyl-2,3-dihydro-1H-1,3-benzodiazol-1-yl)piperidin-1-yl]-2,2-diphenylbutanenitrile
- SMILES
- CCC(=O)N1C(=O)N(C2CCN(CCC(C#N)(C3=CC=CC=C3)C3=CC=CC=C3)CC2)C2=CC=CC=C12
References
- General References
- Meijer DK, Hovinga G, Versluis A, Broring J, van Aken K, Moolenaar F, Wesseling H: Pharmacokinetics of the oral narcotic analgesic bezitramide and preliminary observations on its effect on experimentally induced pain. Eur J Clin Pharmacol. 1984;27(5):615-8. [Article]
- External Links
- PubChem Compound
- 61791
- PubChem Substance
- 46505037
- ChemSpider
- 55675
- ChEBI
- 135794
- ChEMBL
- CHEMBL2104149
- Wikipedia
- Bezitramide
Clinical Trials
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 melting point (°C) 145-149 °C PhysProp water solubility Poor water solubility Meijer, D. K. F., et al. "Pharmacokinetics of the oral narcotic analgesic bezitramide and preliminary observations on its effect on experimentally induced pain." European journal of clinical pharmacology 27.5 (1984): 615-618. logP 4.80 SANGSTER (1993) - Predicted Properties
Property Value Source Water Solubility 0.0067 mg/mL ALOGPS logP 4.35 ALOGPS logP 4.79 Chemaxon logS -4.9 ALOGPS pKa (Strongest Basic) 8.32 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 67.65 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 155.25 m3·mol-1 Chemaxon Polarizability 55.58 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9787 Caco-2 permeable - 0.5631 P-glycoprotein substrate Substrate 0.6446 P-glycoprotein inhibitor I Inhibitor 0.8347 P-glycoprotein inhibitor II Non-inhibitor 0.6466 Renal organic cation transporter Non-inhibitor 0.518 CYP450 2C9 substrate Non-substrate 0.7483 CYP450 2D6 substrate Non-substrate 0.6835 CYP450 3A4 substrate Substrate 0.6644 CYP450 1A2 substrate Non-inhibitor 0.9217 CYP450 2C9 inhibitor Non-inhibitor 0.5586 CYP450 2D6 inhibitor Non-inhibitor 0.7687 CYP450 2C19 inhibitor Non-inhibitor 0.8888 CYP450 3A4 inhibitor Inhibitor 0.584 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6976 Ames test Non AMES toxic 0.569 Carcinogenicity Non-carcinogens 0.8409 Biodegradation Not ready biodegradable 0.9939 Rat acute toxicity 3.5117 LD50, mol/kg Not applicable hERG inhibition (predictor I) Strong inhibitor 0.5527 hERG inhibition (predictor II) Inhibitor 0.6899
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-0000900000-84fdbaa64ec8957a624f Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-0000900000-4063bfc7e042c4876f6b Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-03dl-0000900000-af96b2894cc9bde3a7e3 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-03dl-0001900000-a89441e9120900ee0c99 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-1922700000-51b8154f24baf43e3564 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-4386900000-328e3a08b4203a7716ac 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]- 234.9902765 predictedDarkChem Lite v0.1.0 [M-H]- 211.46355 predictedDeepCCS 1.0 (2019) [M+H]+ 234.6539765 predictedDarkChem Lite v0.1.0 [M+H]+ 213.82155 predictedDeepCCS 1.0 (2019) [M+Na]+ 235.5107765 predictedDarkChem Lite v0.1.0 [M+Na]+ 219.91472 predictedDeepCCS 1.0 (2019)
Drug created at July 31, 2007 13:09 / Updated at February 21, 2021 18:51