Bezitramide

Identification

Name
Bezitramide
Accession Number
DB01459
Type
Small Molecule
Groups
Experimental, Illicit, Withdrawn
Description

Bezitramide is a narcotic analgesic which was discovered in 1961, clinically tested around the 1970's [1], and marketed under the name Burgodin(R). After cases of fatal overdose in the Netherlands in 2004 the drug was withdrawn from the market.

In the United States Bezitramide was never been approved for clinical use. It is presently an illegal substance classified under Schedule II of the Controlled Substances Act. [wiki]

Structure
Thumb
Synonyms
  • 1-[1-(3-Cyano-3,3-diphenylpropyl)-4-piperidinyl]-1,3-dihydro-3-(1-oxopropyl)-2H-benzimidazol-2-one
External IDs
IDS-NB-007 / N02AC05 / R 4845
International/Other Brands
Burgodin (Janssen Pharmceutica)
Categories
UNII
3KXW0Y310I
CAS number
15301-48-1
Weight
Average: 492.6114
Monoisotopic: 492.252526288
Chemical Formula
C31H32N4O2
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

Pharmacology

Indication

A narcotic analgesic once used for the treatment of severe chronic pain. [1]

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
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may increase the analgesic activities of Bezitramide.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may increase the analgesic activities of Bezitramide.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may increase the analgesic activities of Bezitramide.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may increase the analgesic activities of Bezitramide.
AcepromazineAcepromazine may increase the hypotensive activities of Bezitramide.
AceprometazineAceprometazine may increase the hypotensive activities of Bezitramide.
AcetazolamideThe therapeutic efficacy of Acetazolamide can be decreased when used in combination with Bezitramide.
AclidiniumThe risk or severity of adverse effects can be increased when Aclidinium is combined with Bezitramide.
AgmatineThe risk or severity of adverse effects can be increased when Agmatine is combined with Bezitramide.
AlaproclateBezitramide may increase the serotonergic activities of Alaproclate.
Food Interactions
Not Available

References

General References
  1. 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. [PubMed:6519169]
External Links
PubChem Compound
61791
PubChem Substance
46505037
ChemSpider
55675
ChEBI
135794
ChEMBL
CHEMBL2104149
Wikipedia
Bezitramide
ATC Codes
N02AC05 — Bezitramide

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)145-149 °CPhysProp
water solubilityPoor 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.
logP4.80SANGSTER (1993)
Predicted Properties
PropertyValueSource
Water Solubility0.0067 mg/mLALOGPS
logP4.35ALOGPS
logP4.79ChemAxon
logS-4.9ALOGPS
pKa (Strongest Basic)8.32ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area67.65 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity155.25 m3·mol-1ChemAxon
Polarizability55.58 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9787
Caco-2 permeable-0.5631
P-glycoprotein substrateSubstrate0.6446
P-glycoprotein inhibitor IInhibitor0.8347
P-glycoprotein inhibitor IINon-inhibitor0.6466
Renal organic cation transporterNon-inhibitor0.518
CYP450 2C9 substrateNon-substrate0.7483
CYP450 2D6 substrateNon-substrate0.6835
CYP450 3A4 substrateSubstrate0.6644
CYP450 1A2 substrateNon-inhibitor0.9217
CYP450 2C9 inhibitorNon-inhibitor0.5586
CYP450 2D6 inhibitorNon-inhibitor0.7687
CYP450 2C19 inhibitorNon-inhibitor0.8888
CYP450 3A4 inhibitorInhibitor0.584
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6976
Ames testNon AMES toxic0.569
CarcinogenicityNon-carcinogens0.8409
BiodegradationNot ready biodegradable0.9939
Rat acute toxicity3.5117 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.5527
hERG inhibition (predictor II)Inhibitor0.6899
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Diphenylacetonitrile / Diphenylmethane / Benzimidazole / N-acylimidazole / Imidazole-1-carbonyl group / N-acyl urea / Aralkylamine / Ureide / N-substituted imidazole / Piperidine
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Drug created on July 31, 2007 07:09 / Updated on October 01, 2018 13:04