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Identification
NameBezitramide
Accession NumberDB01459
TypeSmall Molecule
GroupsExperimental, Illicit, Withdrawn
DescriptionBezitramide 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 After cases of fatal overdose in the Netherlands in 2004 the drug was withdrawn from the market.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 Identifiers
  • R 4845
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
Burgodin Janssen Pharmceutica
Brand mixturesNot Available
SaltsNot Available
Categories
UNII3KXW0Y310I
CAS number15301-48-1
WeightAverage: 492.6114
Monoisotopic: 492.252526288
Chemical FormulaC31H32N4O2
InChI KeyInChIKey=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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassDiphenylacetonitriles
Direct ParentDiphenylacetonitriles
Alternative Parents
Substituents
  • Diphenylacetonitrile
  • Diphenylmethane
  • Phenylpropylamine
  • Benzyl-cyanide
  • Benzimidazole
  • Aralkylamine
  • 4-aminopiperidine
  • Piperidine
  • N-substituted imidazole
  • Heteroaromatic compound
  • Imidazole
  • Azole
  • Urea
  • Tertiary aliphatic amine
  • Tertiary amine
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Nitrile
  • Carbonitrile
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationA narcotic analgesic once used for the treatment of severe chronic pain. [1]
PharmacodynamicsBezitramide 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 actionNot Available
Related Articles
AbsorptionBezitramide has poor water solubility, thus administration is restricted to the oral route. [1]
Volume of distributionNot Available
Protein bindingNot 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 eliminationLess 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 life11-24h. [1]
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point145-149 °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 FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
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
ATC CodesN02AC05
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may increase the analgesic activities of Bezitramide.
3,4-Methylenedioxymethamphetamine3,4-Methylenedioxymethamphetamine may increase the analgesic activities of Bezitramide.
AcepromazineAcepromazine may increase the hypotensive activities of Bezitramide.
AcetazolamideThe risk or severity of adverse effects can be increased when Bezitramide is combined with Acetazolamide.
AclidiniumThe risk or severity of adverse effects can be increased when Aclidinium is combined with Bezitramide.
AlimemazineAlimemazine may increase the hypotensive activities of Bezitramide.
AlvimopanThe risk or severity of adverse effects can be increased when Bezitramide is combined with Alvimopan.
AmilorideThe risk or severity of adverse effects can be increased when Bezitramide is combined with Amiloride.
Ammonium chlorideAmmonium chloride may increase the excretion rate of Bezitramide which could result in a higher serum level.
AmoxapineBezitramide may increase the serotonergic activities of Amoxapine.
AmphetamineAmphetamine may increase the analgesic activities of Bezitramide.
Anisotropine MethylbromideThe risk or severity of adverse effects can be increased when Anisotropine Methylbromide is combined with Bezitramide.
Atracurium besylateThe risk or severity of adverse effects can be increased when Atracurium besylate is combined with Bezitramide.
AtropineThe risk or severity of adverse effects can be increased when Atropine is combined with Bezitramide.
AzosemideThe risk or severity of adverse effects can be increased when Bezitramide is combined with Azosemide.
BenactyzineThe risk or severity of adverse effects can be increased when Benactyzine is combined with Bezitramide.
BendroflumethiazideThe risk or severity of adverse effects can be increased when Bezitramide is combined with Bendroflumethiazide.
BenzatropineThe risk or severity of adverse effects can be increased when Benzatropine is combined with Bezitramide.
BenzphetamineBenzphetamine may increase the analgesic activities of Bezitramide.
BiperidenThe risk or severity of adverse effects can be increased when Biperiden is combined with Bezitramide.
BumetanideThe risk or severity of adverse effects can be increased when Bezitramide is combined with Bumetanide.
BuprenorphineBuprenorphine may decrease the analgesic activities of Bezitramide.
ButorphanolButorphanol may decrease the analgesic activities of Bezitramide.
Canrenoic acidThe risk or severity of adverse effects can be increased when Bezitramide is combined with Canrenoic acid.
ChlorothiazideThe risk or severity of adverse effects can be increased when Bezitramide is combined with Chlorothiazide.
ChlorphenoxamineThe risk or severity of adverse effects can be increased when Chlorphenoxamine is combined with Bezitramide.
ChlorphentermineChlorphentermine may increase the analgesic activities of Bezitramide.
ChlorpromazineChlorpromazine may increase the hypotensive activities of Bezitramide.
ChlorthalidoneThe risk or severity of adverse effects can be increased when Bezitramide is combined with Chlorthalidone.
CitalopramBezitramide may increase the serotonergic activities of Citalopram.
ClomipramineBezitramide may increase the serotonergic activities of Clomipramine.
ConivaptanThe risk or severity of adverse effects can be increased when Bezitramide is combined with Conivaptan.
CyclopentolateThe risk or severity of adverse effects can be increased when Cyclopentolate is combined with Bezitramide.
CyclothiazideThe risk or severity of adverse effects can be increased when Bezitramide is combined with Cyclothiazide.
DapoxetineBezitramide may increase the serotonergic activities of Dapoxetine.
DarifenacinThe risk or severity of adverse effects can be increased when Darifenacin is combined with Bezitramide.
DesloratadineThe risk or severity of adverse effects can be increased when Desloratadine is combined with Bezitramide.
DesmopressinThe risk or severity of adverse effects can be increased when Bezitramide is combined with Desmopressin.
DexetimideThe risk or severity of adverse effects can be increased when Dexetimide is combined with Bezitramide.
DextroamphetamineDextroamphetamine may increase the analgesic activities of Bezitramide.
DicyclomineThe risk or severity of adverse effects can be increased when Dicyclomine is combined with Bezitramide.
DrospirenoneThe risk or severity of adverse effects can be increased when Bezitramide is combined with Drospirenone.
EfonidipineThe risk or severity of adverse effects can be increased when Bezitramide is combined with Efonidipine.
EluxadolineBezitramide may increase the constipating activities of Eluxadoline.
EplerenoneThe risk or severity of adverse effects can be increased when Bezitramide is combined with Eplerenone.
EscitalopramBezitramide may increase the serotonergic activities of Escitalopram.
Etacrynic acidThe risk or severity of adverse effects can be increased when Bezitramide is combined with Etacrynic acid.
EthopropazineThe risk or severity of adverse effects can be increased when Ethopropazine is combined with Bezitramide.
EthoxzolamideThe risk or severity of adverse effects can be increased when Bezitramide is combined with Ethoxzolamide.
EtoperidoneBezitramide may increase the serotonergic activities of Etoperidone.
FenfluramineBezitramide may increase the serotonergic activities of Fenfluramine.
FesoterodineThe risk or severity of adverse effects can be increased when Fesoterodine is combined with Bezitramide.
FluoxetineBezitramide may increase the serotonergic activities of Fluoxetine.
FluphenazineFluphenazine may increase the hypotensive activities of Bezitramide.
FluvoxamineBezitramide may increase the serotonergic activities of Fluvoxamine.
FurosemideThe risk or severity of adverse effects can be increased when Bezitramide is combined with Furosemide.
Gallamine TriethiodideThe risk or severity of adverse effects can be increased when Gallamine Triethiodide is combined with Bezitramide.
GlycopyrroniumThe risk or severity of adverse effects can be increased when Glycopyrronium is combined with Bezitramide.
HexamethoniumThe risk or severity of adverse effects can be increased when Hexamethonium is combined with Bezitramide.
HomatropineThe risk or severity of adverse effects can be increased when Homatropine is combined with Bezitramide.
HydrochlorothiazideThe risk or severity of adverse effects can be increased when Bezitramide is combined with Hydrochlorothiazide.
HydroflumethiazideThe risk or severity of adverse effects can be increased when Bezitramide is combined with Hydroflumethiazide.
Hydroxyamphetamine hydrobromideHydroxyamphetamine hydrobromide may increase the analgesic activities of Bezitramide.
HyoscyamineThe risk or severity of adverse effects can be increased when Hyoscyamine is combined with Bezitramide.
IndalpineBezitramide may increase the serotonergic activities of Indalpine.
IndapamideThe risk or severity of adverse effects can be increased when Bezitramide is combined with Indapamide.
Ipratropium bromideThe risk or severity of adverse effects can be increased when Ipratropium bromide is combined with Bezitramide.
IsosorbideThe risk or severity of adverse effects can be increased when Bezitramide is combined with Isosorbide.
KW-3902The risk or severity of adverse effects can be increased when Bezitramide is combined with KW-3902.
LevomilnacipranBezitramide may increase the serotonergic activities of Levomilnacipran.
LisdexamfetamineLisdexamfetamine may increase the analgesic activities of Bezitramide.
Lu AA21004Bezitramide may increase the serotonergic activities of Lu AA21004.
MannitolThe risk or severity of adverse effects can be increased when Bezitramide is combined with Mannitol.
MecamylamineThe risk or severity of adverse effects can be increased when Mecamylamine is combined with Bezitramide.
MephentermineMephentermine may increase the analgesic activities of Bezitramide.
MersalylThe risk or severity of adverse effects can be increased when Bezitramide is combined with Mersalyl.
MesoridazineMesoridazine may increase the hypotensive activities of Bezitramide.
MethamphetamineMethamphetamine may increase the analgesic activities of Bezitramide.
MethanthelineThe risk or severity of adverse effects can be increased when Methantheline is combined with Bezitramide.
MethazolamideThe risk or severity of adverse effects can be increased when Bezitramide is combined with Methazolamide.
MethotrimeprazineMethotrimeprazine may increase the hypotensive activities of Bezitramide.
MethyclothiazideThe risk or severity of adverse effects can be increased when Bezitramide is combined with Methyclothiazide.
Methylene blueMethylene blue may increase the hypotensive activities of Bezitramide.
MetixeneThe risk or severity of adverse effects can be increased when Metixene is combined with Bezitramide.
MetolazoneThe risk or severity of adverse effects can be increased when Bezitramide is combined with Metolazone.
MilnacipranBezitramide may increase the serotonergic activities of Milnacipran.
MoricizineMoricizine may increase the hypotensive activities of Bezitramide.
N-butylscopolammonium bromideThe risk or severity of adverse effects can be increased when N-butylscopolammonium bromide is combined with Bezitramide.
NalbuphineNalbuphine may decrease the analgesic activities of Bezitramide.
NaltrexoneThe therapeutic efficacy of Bezitramide can be decreased when used in combination with Naltrexone.
NVA237The risk or severity of adverse effects can be increased when NVA237 is combined with Bezitramide.
OlanzapineBezitramide may increase the serotonergic activities of Olanzapine.
OrphenadrineThe risk or severity of adverse effects can be increased when Orphenadrine is combined with Bezitramide.
OxybutyninThe risk or severity of adverse effects can be increased when Oxybutynin is combined with Bezitramide.
OxyphenoniumThe risk or severity of adverse effects can be increased when Oxyphenonium is combined with Bezitramide.
PancuroniumThe risk or severity of adverse effects can be increased when Pancuronium is combined with Bezitramide.
ParoxetineBezitramide may increase the serotonergic activities of Paroxetine.
PegvisomantThe therapeutic efficacy of Pegvisomant can be decreased when used in combination with Bezitramide.
PentazocinePentazocine may decrease the analgesic activities of Bezitramide.
PentoliniumThe risk or severity of adverse effects can be increased when Pentolinium is combined with Bezitramide.
PerphenazinePerphenazine may increase the hypotensive activities of Bezitramide.
PhenterminePhentermine may increase the analgesic activities of Bezitramide.
PipecuroniumThe risk or severity of adverse effects can be increased when Pipecuronium is combined with Bezitramide.
PirenzepineThe risk or severity of adverse effects can be increased when Pirenzepine is combined with Bezitramide.
PiretanideThe risk or severity of adverse effects can be increased when Bezitramide is combined with Piretanide.
PolythiazideThe risk or severity of adverse effects can be increased when Bezitramide is combined with Polythiazide.
PotassiumThe risk or severity of adverse effects can be increased when Bezitramide is combined with Potassium.
Potassium CitrateThe risk or severity of adverse effects can be increased when Bezitramide is combined with Potassium Citrate.
ProchlorperazineProchlorperazine may increase the hypotensive activities of Bezitramide.
ProcyclidineThe risk or severity of adverse effects can be increased when Procyclidine is combined with Bezitramide.
PromazinePromazine may increase the hypotensive activities of Bezitramide.
PromethazinePromethazine may increase the hypotensive activities of Bezitramide.
PropanthelineThe risk or severity of adverse effects can be increased when Propantheline is combined with Bezitramide.
QuinethazoneThe risk or severity of adverse effects can be increased when Bezitramide is combined with Quinethazone.
QuinidineThe risk or severity of adverse effects can be increased when Quinidine is combined with Bezitramide.
RamosetronBezitramide may increase the constipating activities of Ramosetron.
ScopolamineThe risk or severity of adverse effects can be increased when Scopolamine is combined with Bezitramide.
Scopolamine butylbromideThe risk or severity of adverse effects can be increased when Scopolamine butylbromide is combined with Bezitramide.
SertralineBezitramide may increase the serotonergic activities of Sertraline.
SolifenacinThe risk or severity of adverse effects can be increased when Solifenacin is combined with Bezitramide.
SpironolactoneThe risk or severity of adverse effects can be increased when Bezitramide is combined with Spironolactone.
SuccinylcholineSuccinylcholine may increase the bradycardic activities of Bezitramide.
TheobromineThe risk or severity of adverse effects can be increased when Bezitramide is combined with Theobromine.
ThiethylperazineThiethylperazine may increase the hypotensive activities of Bezitramide.
ThioridazineThioridazine may increase the hypotensive activities of Bezitramide.
TicrynafenThe risk or severity of adverse effects can be increased when Bezitramide is combined with Ticrynafen.
TiotropiumThe risk or severity of adverse effects can be increased when Tiotropium is combined with Bezitramide.
TolterodineThe risk or severity of adverse effects can be increased when Tolterodine is combined with Bezitramide.
TolvaptanThe risk or severity of adverse effects can be increased when Bezitramide is combined with Tolvaptan.
TorasemideThe risk or severity of adverse effects can be increased when Bezitramide is combined with Torasemide.
TrazodoneBezitramide may increase the serotonergic activities of Trazodone.
TriamtereneThe risk or severity of adverse effects can be increased when Bezitramide is combined with Triamterene.
TrichlormethiazideThe risk or severity of adverse effects can be increased when Bezitramide is combined with Trichlormethiazide.
TrifluoperazineTrifluoperazine may increase the hypotensive activities of Bezitramide.
TriflupromazineTriflupromazine may increase the hypotensive activities of Bezitramide.
TrihexyphenidylThe risk or severity of adverse effects can be increased when Trihexyphenidyl is combined with Bezitramide.
TrimethaphanThe risk or severity of adverse effects can be increased when Trimethaphan is combined with Bezitramide.
TropicamideThe risk or severity of adverse effects can be increased when Tropicamide is combined with Bezitramide.
TrospiumThe risk or severity of adverse effects can be increased when Trospium is combined with Bezitramide.
TubocurarineThe risk or severity of adverse effects can be increased when Tubocurarine is combined with Bezitramide.
UlaritideThe risk or severity of adverse effects can be increased when Bezitramide is combined with Ularitide.
UmeclidiniumThe risk or severity of adverse effects can be increased when Umeclidinium is combined with Bezitramide.
VecuroniumThe risk or severity of adverse effects can be increased when Vecuronium is combined with Bezitramide.
VilazodoneBezitramide may increase the serotonergic activities of Vilazodone.
VortioxetineBezitramide may increase the serotonergic activities of Vortioxetine.
ZimelidineBezitramide may increase the serotonergic activities of Zimelidine.
Food InteractionsNot Available
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Drug created on July 31, 2007 07:09 / Updated on August 17, 2016 12:23