Identification

Name
Oxetacaine
Accession Number
DB12532
Type
Small Molecule
Groups
Approved, Investigational
Description

Oxetacaine, also called oxethazaince, is a potent surface analgesic with the molecular formula N, N-bis-(N-methyl-N-phenyl-t-butyl-acetamide)-beta-hydroxyethylamine that conserves its unionized form at low pH levels. Its actions have shown to relieve dysphagia, relieve pain due to reflux, chronic gastritis, and duodenal ulcer.[1] Oxetacaine is approved by Health Canada since 1995 for its use as an antacid combination in over-the-counter preparations.[6] It is also in the list of approved derivatives of herbal products by the EMA.[7]

Structure
Thumb
Synonyms
  • Oxetacaine
External IDs
WY-806
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Mucaine - SusOxetacaine (10 mg) + Aluminum hydroxide (300 mg) + Magnesium hydroxide (100 mg)SuspensionOralAurium Pharma Inc1995-12-31Not applicableCanada
Categories
UNII
IP8QT76V17
CAS number
126-27-2
Weight
Average: 467.654
Monoisotopic: 467.314792192
Chemical Formula
C28H41N3O3
InChI Key
FTLDJPRFCGDUFH-UHFFFAOYSA-N
InChI
InChI=1S/C28H41N3O3/c1-27(2,19-23-13-9-7-10-14-23)29(5)25(33)21-31(17-18-32)22-26(34)30(6)28(3,4)20-24-15-11-8-12-16-24/h7-16,32H,17-22H2,1-6H3
IUPAC Name
2-[(2-hydroxyethyl)({[methyl(2-methyl-1-phenylpropan-2-yl)carbamoyl]methyl})amino]-N-methyl-N-(2-methyl-1-phenylpropan-2-yl)acetamide
SMILES
CN(C(=O)CN(CCO)CC(=O)N(C)C(C)(C)CC1=CC=CC=C1)C(C)(C)CC1=CC=CC=C1

Pharmacology

Indication

Oxetacaine is available as an over-the-counter antacid and it is used to alleviate pain associated with gastritis, peptic ulcer disease, heartburn, esophagitis, hiatus hernia, and anorexia.[3]

Associated Conditions
Pharmacodynamics

Oxetacaine improves common gastrointestinal symptoms.[3] Oxetacaine is part of the anesthetic antacids which increase the gastric pH while providing relief from pain for a longer period of duration at a lower dosage. This property has been reported to relieve the symptoms of hyperacidity. Oxetacaine is reported to produce a reversible loss of sensation and to provide a prompt and prolonged relief of pain. In vitro, oxetacaine was showed to produce an antispasmodic action on the smooth muscle and block the action of serotonin.[4]

The local efficacy of oxetacaine has been proven to be 2000 times more potent than lignocaine and 500 times more potent than cocaine. Its anesthetic action produces the loss of sensation which can be explained by its inhibitory activity against the nerve impulses and de decrease in permeability of the cell membrane.[4]

Mechanism of action

Oxetacaine inhibits gastric acid secretion by suppressing gastrin secretion.[3]

Moreover, oxetacaine exerts a local anesthetic effect on the gastric mucosa. This potent local anesthetic effect of oxetacaine may be explained by its unique chemical characteristics in which, as a weak base, it is relatively non-ionized in acidic solutions whereas its hydrochloride salt is soluble in organic solvents and it can penetrate cell membranes.[2] Oxetacaine diminishes the conduction of sensory nerve impulses near the application site which in order reduces the permeability of the cell membrane to sodium ions.[4] This activity is performed by the incorporation of the unionized form into the cell membrane.[5]

TargetActionsOrganism
AGastrin
inhibition of synthesis
Human
Absorption

A peak plasma concentration of oxetacaine of approximately 20 ng/ml is attained about one hour after oral administration.[4] LEss than 1/3 of the administered dose is absorbed as it undergoes extensive metabolism.[5]

Volume of distribution

This pharmacokinetic property has not been studied.

Protein binding

Due to the low half-life, it is thought that oxetacaine, when absorbed, presents a very low protein plasma binding.[5]

Metabolism

Oxetacaine is rapidly and extensively metabolized hepatically. After metabolism, there is a formation of primary metabolites such as beta-hydroxy-mephentermine and beta-hydroxy-phentermine. The major metabolites are found in the plasma in insignificant amounts.[4]

Route of elimination

Less than 0.1% of the amdinistered dose is recovered in urine within 24 hours in the form of unchanged oxetacaine or its metabolites.[4]

Half life

Oxetacaine presents a very short half-life of approximately one hour.[4]

Clearance

This pharmacokinetic property has not been studied.

Toxicity

When orally administered, oxetacaine presents a good tolerance. However, following intravenous injection, oxetacaine toxicity is high and it is presented as a depression in myocardial contractility and impaired conduction.[2]

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

Interactions

Drug Interactions
DrugInteractionDrug group
AsunaprevirThe serum concentration of Asunaprevir can be increased when it is combined with Oxetacaine.Approved, Investigational, Withdrawn
AtorvastatinThe risk or severity of adverse effects can be increased when Oxetacaine is combined with Atorvastatin.Approved
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Oxetacaine.Approved
BromocriptineThe risk or severity of adverse effects can be increased when Bromocriptine is combined with Oxetacaine.Approved, Investigational
CabergolineThe risk or severity of adverse effects can be increased when Cabergoline is combined with Oxetacaine.Approved
CerivastatinThe serum concentration of Cerivastatin can be increased when it is combined with Oxetacaine.Approved, Withdrawn
DihydroergocornineThe risk or severity of adverse effects can be increased when Dihydroergocornine is combined with Oxetacaine.Approved
DihydroergocristineThe risk or severity of adverse effects can be increased when Dihydroergocristine is combined with Oxetacaine.Approved, Experimental
DihydroergocryptineThe risk or severity of adverse effects can be increased when Dihydroergocryptine is combined with Oxetacaine.Experimental
DihydroergotamineThe risk or severity of adverse effects can be increased when Dihydroergotamine is combined with Oxetacaine.Approved, Investigational
ErgonovineThe risk or severity of adverse effects can be increased when Ergonovine is combined with Oxetacaine.Approved
ErgotamineThe risk or severity of adverse effects can be increased when Ergotamine is combined with Oxetacaine.Approved
HyaluronidaseThe risk or severity of adverse effects can be increased when Hyaluronidase is combined with Oxetacaine.Approved, Investigational
IbrutinibThe serum concentration of Ibrutinib can be increased when it is combined with Oxetacaine.Approved
LisurideThe risk or severity of adverse effects can be increased when Lisuride is combined with Oxetacaine.Approved, Investigational
LovastatinThe serum concentration of Lovastatin can be increased when it is combined with Oxetacaine.Approved, Investigational
Lysergic Acid DiethylamideThe risk or severity of adverse effects can be increased when Lysergic Acid Diethylamide is combined with Oxetacaine.Illicit, Investigational, Withdrawn
MetergolineThe risk or severity of adverse effects can be increased when Metergoline is combined with Oxetacaine.Experimental
MethylergometrineThe risk or severity of adverse effects can be increased when Methylergometrine is combined with Oxetacaine.Approved
MethysergideThe risk or severity of adverse effects can be increased when Methysergide is combined with Oxetacaine.Approved
MevastatinThe serum concentration of Mevastatin can be increased when it is combined with Oxetacaine.Experimental
NicergolineThe risk or severity of adverse effects can be increased when Nicergoline is combined with Oxetacaine.Approved, Investigational
PergolideThe risk or severity of adverse effects can be increased when Pergolide is combined with Oxetacaine.Approved, Investigational, Vet Approved, Withdrawn
PitavastatinThe serum concentration of Pitavastatin can be increased when it is combined with Oxetacaine.Approved
PravastatinThe serum concentration of Pravastatin can be increased when it is combined with Oxetacaine.Approved
RilpivirineThe serum concentration of Rilpivirine can be increased when it is combined with Oxetacaine.Approved
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Oxetacaine.Approved
Technetium Tc-99m tilmanoceptOxetacaine may decrease effectiveness of Technetium Tc-99m tilmanocept as a diagnostic agent.Approved, Investigational
TergurideThe risk or severity of adverse effects can be increased when Terguride is combined with Oxetacaine.Experimental
TolvaptanThe serum concentration of Tolvaptan can be increased when it is combined with Oxetacaine.Approved
Food Interactions
Not Available

References

General References
  1. BALMFORTH GV, SAMUEL RK: CONTROLLED TRIAL OF OXETHAZAINE AS AN ANALGESIC IN DUODENAL ULCER. Br Med J. 1964 Feb 8;1(5379):355-6. [PubMed:14079039]
  2. Masuda Y, Yoshizawa T, Ozaki M, Tanaka T: The metabolic and hemodynamic effects of oxethazaine in the perfused rat liver. Jpn J Pharmacol. 1996 Mar;70(3):243-52. [PubMed:8935718]
  3. Namba H, Nishimura Y, Kurata N, Iwase M, Hirai T, Kiuchi Y: Inhibitory Effect of Oxethazaine on Midazolam Metabolism in Rats. Biol Pharm Bull. 2017;40(9):1361-1365. doi: 10.1248/bpb.b16-01016. [PubMed:28867721]
  4. Parakh R. and Patil N. (2017). International Journal of Research in Medical Sciences. MSJ Online.
  5. Kapoor A. and Raju S. (2013). Ilustrated Medical Pharmacology. Jaypee Brothers. [ISBN:978-93-5090-655-2]
  6. Health Canada [Link]
  7. EMA Herbal substances [Link]
External Links
KEGG Compound
C12552
PubChem Compound
4621
PubChem Substance
347828759
ChemSpider
4460
BindingDB
50017672
ChEBI
31947
ChEMBL
CHEMBL127592
Wikipedia
Oxetacaine
ATC Codes
C05AD06 — Oxetacaine
MSDS
Download (276 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3TerminatedTreatmentRadiation-induced Oesophagitis1

Pharmacoeconomics

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

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)100-101 ºC'MSDS'
boiling point (°C)630 ºC at 760 mm Hg'MSDS'
water solubility<0.1 g/100 ml at 23 ºC'MSDS'
pKa6.25Posey E., Boler K. and Posey L. The Amerian Journal of Digestive Diseases. (1969)
Predicted Properties
PropertyValueSource
Water Solubility0.0102 mg/mLALOGPS
logP3.67ALOGPS
logP3.16ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)15.59ChemAxon
pKa (Strongest Basic)5.78ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area64.09 Å2ChemAxon
Rotatable Bond Count12ChemAxon
Refractivity138.53 m3·mol-1ChemAxon
Polarizability52.95 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

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
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-4921100000-a1f5b0f2bfd88a9426a7

Taxonomy

Description
This compound belongs to the class of organic compounds known as amphetamines and derivatives. These are organic compounds containing or derived from 1-phenylpropan-2-amine.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Phenethylamines
Direct Parent
Amphetamines and derivatives
Alternative Parents
Alpha amino acids and derivatives / Phenylpropanes / Tertiary carboxylic acid amides / Trialkylamines / 1,2-aminoalcohols / Primary alcohols / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Alpha-amino acid or derivatives / Amphetamine or derivatives / Phenylpropane / Tertiary carboxylic acid amide / 1,2-aminoalcohol / Amino acid or derivatives / Carboxamide group / Tertiary amine / Tertiary aliphatic amine / Carboxylic acid derivative
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
amino acid amide (CHEBI:31947)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibition of synthesis
General Function
Gastrin stimulates the stomach mucosa to produce and secrete hydrochloric acid and the pancreas to secrete its digestive enzymes. It also stimulates smooth muscle contraction and increases blood circulation and water secretion in the stomach and intestine.
Specific Function
Hormone activity
Gene Name
GAST
Uniprot ID
P01350
Uniprot Name
Gastrin
Molecular Weight
11393.63 Da
References
  1. Namba H, Nishimura Y, Kurata N, Iwase M, Hirai T, Kiuchi Y: Inhibitory Effect of Oxethazaine on Midazolam Metabolism in Rats. Biol Pharm Bull. 2017;40(9):1361-1365. doi: 10.1248/bpb.b16-01016. [PubMed:28867721]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Parakh R. and Patil N. (2017). International Journal of Research in Medical Sciences. MSJ Online.

Drug created on October 20, 2016 16:45 / Updated on August 02, 2018 06:40