Identification

Name
Benzquinamide
Accession Number
DB00767  (APRD00820)
Type
Small Molecule
Groups
Withdrawn
Description

Benzquinamide is a discontinued antiemetic compound with antihistaminic, mild anticholinergic, and sedative properties. The mechanism of action is not known, but presumably benzquinamide works via antagonism of muscarinic acetycholine receptors and histamine H1 receptors.

Structure
Thumb
Synonyms
  • BZQ
Product Ingredients
IngredientUNIICASInChI Key
Benzquinamide hydrochloride3221WFM86J113-69-9KZLNXGBVFTWMPS-UHFFFAOYSA-N
International/Other Brands
Benzchinamide / Emete-con (Pfizer) / Emeticon (Pfizer) / Promecon (Endo) / Quantril (Pfizer)
Categories
UNII
0475EA27Q3
CAS number
63-12-7
Weight
Average: 404.4999
Monoisotopic: 404.231122144
Chemical Formula
C22H32N2O5
InChI Key
JSZILQVIPPROJI-UHFFFAOYSA-N
InChI
InChI=1S/C22H32N2O5/c1-6-23(7-2)22(26)17-13-24-9-8-15-10-20(27-4)21(28-5)11-16(15)18(24)12-19(17)29-14(3)25/h10-11,17-19H,6-9,12-13H2,1-5H3
IUPAC Name
3-(diethylcarbamoyl)-9,10-dimethoxy-1H,2H,3H,4H,6H,7H,11bH-pyrido[2,1-a]isoquinolin-2-yl acetate
SMILES
CCN(CC)C(=O)C1CN2CCC3=CC(OC)=C(OC)C=C3C2CC1OC(C)=O

Pharmacology

Indication

Used to prevent and treat nausea and vomiting associated with anesthesia and surgery, administered intramuscularly or intravenously.

Pharmacodynamics

Benzquinamide is an antiemetic compound with antihistaminic, mild anticholinergic, and sedative properties.

Mechanism of action

The mechanism of action is not known, but presumably benzquinamide works via antagonism of muscarinic acetycholine receptors and histamine H1 receptors.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
Human
AMuscarinic acetylcholine receptor M4
antagonist
Human
AMuscarinic acetylcholine receptor M1
antagonist
Human
AMuscarinic acetylcholine receptor M5
antagonist
Human
AMuscarinic acetylcholine receptor M2
antagonist
Human
AMuscarinic acetylcholine receptor M3
antagonist
Human
Absorption

Incomplete, with 33–39% bioavailability via the capsule and suppository routes, relative to the intramuscular route.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

1-1.6 hours (for all formulations)

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative activities of Benzquinamide.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative activities of Benzquinamide.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative activities of Benzquinamide.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative activities of Benzquinamide.
AcebutololThe serum concentration of Acebutolol can be increased when it is combined with Benzquinamide.
Acetylsalicylic acidThe serum concentration of Acetylsalicylic acid can be increased when it is combined with Benzquinamide.
AgmatineThe risk or severity of adverse effects can be increased when Benzquinamide is combined with Agmatine.
AmitriptylineThe serum concentration of Amitriptyline can be increased when it is combined with Benzquinamide.
AmphetamineAmphetamine may decrease the sedative and stimulatory activities of Benzquinamide.
Ascorbic acidThe serum concentration of Ascorbic acid can be increased when it is combined with Benzquinamide.
Food Interactions
Not Available

References

Synthesis Reference

Tretter, J.R.; US. Patent 3,053,845; September 11, 1962; assigned to Chas. Pfizer & Co., Inc. Lombardino, J.G. and McLamore, W.M.; U.S. Patent 3,055,894; September 25,1962; assigned to Chas. Pfizer & Co., Inc.

General References
Not Available
External Links
Human Metabolome Database
HMDB0014905
KEGG Drug
D00243
PubChem Compound
2342
PubChem Substance
46506155
ChemSpider
2252
ChEBI
27662
ChEMBL
CHEMBL1201250
Therapeutic Targets Database
DAP000713
PharmGKB
PA164749018
Wikipedia
Benzquinamide

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Pfizer inc
  • Roerig div pfizer inc
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)130-131.5Tretter, J.R.; US. Patent 3,053,845; September 11, 1962;assigned to Chas. Pfizer & Co., Inc. Lombardino, J.G. and McLamore, W.M.; U.S. Patent 3,055,894; September 25,1962; assigned to Chas. Pfizer & Co., Inc.
water solubility153 mg/LNot Available
logP1.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.49 mg/mLALOGPS
logP2.49ALOGPS
logP1.42ChemAxon
logS-2.9ALOGPS
pKa (Strongest Acidic)19.61ChemAxon
pKa (Strongest Basic)7.5ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area68.31 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity110.47 m3·mol-1ChemAxon
Polarizability45.27 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8998
Blood Brain Barrier+0.9383
Caco-2 permeable+0.6206
P-glycoprotein substrateSubstrate0.7763
P-glycoprotein inhibitor IInhibitor0.7325
P-glycoprotein inhibitor IINon-inhibitor0.5791
Renal organic cation transporterNon-inhibitor0.5858
CYP450 2C9 substrateNon-substrate0.8588
CYP450 2D6 substrateNon-substrate0.7872
CYP450 3A4 substrateSubstrate0.7516
CYP450 1A2 substrateNon-inhibitor0.8882
CYP450 2C9 inhibitorNon-inhibitor0.9501
CYP450 2D6 inhibitorNon-inhibitor0.9311
CYP450 2C19 inhibitorNon-inhibitor0.7941
CYP450 3A4 inhibitorNon-inhibitor0.8742
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7716
Ames testNon AMES toxic0.7011
CarcinogenicityNon-carcinogens0.8844
BiodegradationNot ready biodegradable0.9795
Rat acute toxicity2.5546 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9392
hERG inhibition (predictor II)Inhibitor0.5894
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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 tetrahydroisoquinolines. These are tetrahydrogenated isoquinoline derivatives.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Tetrahydroisoquinolines
Sub Class
Not Available
Direct Parent
Tetrahydroisoquinolines
Alternative Parents
Piperidinecarboxamides / Anisoles / Aralkylamines / Alkyl aryl ethers / Tertiary carboxylic acid amides / Trialkylamines / Carboxylic acid esters / Amino acids and derivatives / Monocarboxylic acids and derivatives / Azacyclic compounds
show 4 more
Substituents
Tetrahydroisoquinoline / 3-piperidinecarboxamide / Piperidinecarboxamide / Anisole / Alkyl aryl ether / Aralkylamine / Benzenoid / Piperidine / Tertiary carboxylic acid amide / Tertiary aliphatic amine
show 18 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
monocarboxylic acid amide (CHEBI:27662)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Histamine receptor activity
Specific Function
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
References
  1. 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]
  2. 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]
  3. Maurer H, Pfleger K: Identification and differentiation of alkylamine antihistamines and their metabolites in urine by computerized gas chromatography-mass spectrometry. J Chromatogr. 1988 Aug 19;430(1):31-41. [PubMed:2905706]
  4. Niemegeers CJ: Antiemetic specificity of dopamine antagonists. Psychopharmacology (Berl). 1982;78(3):210-3. [PubMed:6130555]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Guanyl-nucleotide exchange factor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM4
Uniprot ID
P08173
Uniprot Name
Muscarinic acetylcholine receptor M4
Molecular Weight
53048.65 Da
References
  1. 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]
  2. 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]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 Da
References
  1. 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]
  2. 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]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM5
Uniprot ID
P08912
Uniprot Name
Muscarinic acetylcholine receptor M5
Molecular Weight
60073.205 Da
References
  1. 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]
  2. 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]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
G-protein coupled acetylcholine receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM2
Uniprot ID
P08172
Uniprot Name
Muscarinic acetylcholine receptor M2
Molecular Weight
51714.605 Da
References
  1. 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]
  2. 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]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM3
Uniprot ID
P20309
Uniprot Name
Muscarinic acetylcholine receptor M3
Molecular Weight
66127.445 Da
References
  1. 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]
  2. 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]

Drug created on June 13, 2005 07:24 / Updated on August 02, 2018 07:53