Identification

Summary

Doxapram is a short acting respiratory stimulant used to treat acute respiratory insufficiency in COPD patients.

Brand Names
Dopram
Generic Name
Doxapram
DrugBank Accession Number
DB00561
Background

A central respiratory stimulant with a brief duration of action. (From Martindale, The Extra Pharmocopoeia, 30th ed, p1225)

Type
Small Molecule
Groups
Approved, Vet approved
Structure
Thumb
Weight
Average: 378.5072
Monoisotopic: 378.230728214
Chemical Formula
C24H30N2O2
Synonyms
  • (±)-doxapram
  • 1-ethyl-4-(2-morpholinoethyl)-3,3-diphenyl-2-pyrrolidinone
  • Doxapram
  • Doxapramum

Pharmacology

Indication

For use as a temporary measure in hospitalized patients with acute respiratory insufficiency superimposed on chronic obstructive pulmonary disease.

Pharmacology
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Associated Conditions
Associated Therapies
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Doxapram is an analeptic agent (a stimulant of the central nervous system). The respiratory stimulant action is manifested by an increase in tidal volume associated with a slight increase in respiratory rate. A pressor response may result following doxapram administration. Provided there is no impairment of cardiac function, the pressor effect is more marked in hypovolemic than in normovolemic states. The pressor response is due to the improved cardiac output rather than peripheral vasoconstriction. Following doxapram administration, an increased release of catecholamines has been noted.

Mechanism of action

Doxapram produces respiratory stimulation mediated through the peripheral carotid chemoreceptors. It is thought to stimulate the carotid body by inhibiting certain potassium channels.

TargetActionsOrganism
APotassium channel subfamily K member 3
inhibitor
Humans
APotassium channel subfamily K member 9
inhibitor
Humans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
Adverseeffects
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Toxicity

Intravenous LD50 values in the mouse and rat were approximately 75 mg/kg and in the cat and dog were 40 to 80 mg/kg. Symptoms of overdosage are extensions of the pharmacologic effects of the drug. Excessive pressor effect, tachycardia, skeletal muscle hyperactivity, and enhanced deep tendon reflexes may be early signs of overdosage.

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.
DrugInteraction
AcebutololDoxapram may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of hypertension can be increased when Doxapram is combined with Aceclofenac.
AcemetacinThe risk or severity of hypertension can be increased when Doxapram is combined with Acemetacin.
Acetylsalicylic acidThe risk or severity of hypertension can be increased when Doxapram is combined with Acetylsalicylic acid.
AlclofenacThe risk or severity of hypertension can be increased when Doxapram is combined with Alclofenac.
AlfentanilThe risk or severity of hypertension can be increased when Doxapram is combined with Alfentanil.
AliskirenDoxapram may decrease the antihypertensive activities of Aliskiren.
AlmotriptanThe risk or severity of hypertension can be increased when Doxapram is combined with Almotriptan.
AmbrisentanDoxapram may decrease the antihypertensive activities of Ambrisentan.
AminophenazoneThe risk or severity of hypertension can be increased when Doxapram is combined with Aminophenazone.
Interactions
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Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Doxapram hydrochlorideP5RU6UOQ5Y7081-53-0ZOMBFZRWMLIDPX-UHFFFAOYSA-N
International/Other Brands
Caropram (Khandelwal) / Dai Er Song (Bosen Bio Pharmaceutical) / Jia Su Lun (Nhwa) / Stimulex / Ze Lun (Jiuxu Pharmaceutical)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
DopramInjection20 mg/1mLIntravenousHikma Pharmaceuticals USA Inc.1965-06-23Not applicableUS flag
DopramInjection20 mg/1mLIntravenousBaxter Laboratories2010-11-292013-06-30US flag
Dopram Inj 20mg/mlLiquid20 mg / mLIntravenousAyerst Laboratories1992-12-311996-09-10Canada flag
Dopram Injectable Liq 20mg/mlLiquid20 mg / mLIntravenousWyeth Ayerst Canada Inc.1994-12-312001-04-23Canada flag
Doxapram HydrochlorideInjection20 mg/1mLIntravenousHF Acquisition Co LLC, DBA HealthFirst2019-10-19Not applicableUS flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Doxapram HydrochlorideInjection20 mg/1mLIntravenousBedford Pharmaceuticals2003-02-102011-12-31US flag

Categories

ATC Codes
R07AB01 — Doxapram
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Diphenylmethanes
Direct Parent
Diphenylmethanes
Alternative Parents
Phenylpyrrolidines / Aralkylamines / Morpholines / N-alkylpyrrolidines / Pyrrolidine-2-ones / Tertiary carboxylic acid amides / Pyrroles / Trialkylamines / Amino acids and derivatives / Lactams
show 7 more
Substituents
2-pyrrolidone / 3-phenylpyrrolidine / Amine / Amino acid or derivatives / Aralkylamine / Aromatic heteromonocyclic compound / Azacycle / Carbonyl group / Carboxamide group / Carboxylic acid derivative
show 22 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
morpholines, pyrrolidin-2-ones (CHEBI:681848)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
94F3830Q73
CAS number
309-29-5
InChI Key
XFDJYSQDBULQSI-UHFFFAOYSA-N
InChI
InChI=1S/C24H30N2O2/c1-2-26-19-22(13-14-25-15-17-28-18-16-25)24(23(26)27,20-9-5-3-6-10-20)21-11-7-4-8-12-21/h3-12,22H,2,13-19H2,1H3
IUPAC Name
1-ethyl-4-[2-(morpholin-4-yl)ethyl]-3,3-diphenylpyrrolidin-2-one
SMILES
CCN1CC(CCN2CCOCC2)C(C1=O)(C1=CC=CC=C1)C1=CC=CC=C1

References

Synthesis Reference

Lunsford, C.D. and Cale, A.D. Jr.; U S . Patent 3,192,230; June 29, 1965; assigned to A.H. Robins Company, Inc.

General References
  1. Singh P, Dimitriou V, Mahajan RP, Crossley AW: Double-blind comparison between doxapram and pethidine in the treatment of postanaesthetic shivering. Br J Anaesth. 1993 Nov;71(5):685-8. [Article]
  2. Yost CS: A new look at the respiratory stimulant doxapram. CNS Drug Rev. 2006 Fall-Winter;12(3-4):236-49. [Article]
Human Metabolome Database
HMDB0014701
KEGG Drug
D07873
PubChem Compound
3156
PubChem Substance
46506829
ChemSpider
3044
BindingDB
50505297
RxNav
3637
ChEBI
681848
ChEMBL
CHEMBL1754
Therapeutic Targets Database
DAP001295
PharmGKB
PA164784026
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Doxapram
FDA label
Download (224 KB)
MSDS
Download (50.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedSupportive CareHypoxia / Sedation1
4CompletedTreatmentApnea / Infants, Premature1
3RecruitingTreatmentPrimary apnea of premature newborns / Respiratory Insufficiency1
2CompletedTreatmentAnaesthesia1
2CompletedTreatmentTreatment of Induced Panic Attack1
Not AvailableRecruitingSupportive CareWeaning Failure1
Not AvailableUnknown StatusTreatmentAnaesthesia therapy1

Pharmacoeconomics

Manufacturers
  • Baxter healthcare corp anesthesia and critical care
  • Bedford laboratories div ben venue laboratories inc
  • Watson laboratories inc
Packagers
  • Baxter International Inc.
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Modern Veterinary Therapeutics LLC
Dosage Forms
FormRouteStrength
LiquidIntravenous20 mg / mL
InjectionIntravenous20 mg/1mL
Injection, solutionIntravenous
Prices
Unit descriptionCostUnit
Doxapram hcl 20 mg/ml vial4.67USD ml
Dopram 20 mg/ml vial2.52USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)217-219Lunsford, C.D. and Cale, A.D. Jr.; U S . Patent 3,192,230; June 29, 1965; assigned to A.H. Robins Company, Inc.
water solubilitySparingly solubleNot Available
logP3.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0343 mg/mLALOGPS
logP3.65ALOGPS
logP3.23ChemAxon
logS-4ALOGPS
pKa (Strongest Basic)7.23ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area32.78 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity112.85 m3·mol-1ChemAxon
Polarizability43.02 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9877
Caco-2 permeable+0.6673
P-glycoprotein substrateSubstrate0.7033
P-glycoprotein inhibitor IInhibitor0.8564
P-glycoprotein inhibitor IINon-inhibitor0.7037
Renal organic cation transporterNon-inhibitor0.5199
CYP450 2C9 substrateNon-substrate0.7735
CYP450 2D6 substrateNon-substrate0.7295
CYP450 3A4 substrateSubstrate0.6409
CYP450 1A2 substrateNon-inhibitor0.6917
CYP450 2C9 inhibitorNon-inhibitor0.8071
CYP450 2D6 inhibitorNon-inhibitor0.7945
CYP450 2C19 inhibitorNon-inhibitor0.7838
CYP450 3A4 inhibitorNon-inhibitor0.5697
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7109
Ames testNon AMES toxic0.8198
CarcinogenicityNon-carcinogens0.8969
BiodegradationNot ready biodegradable0.9931
Rat acute toxicity3.1933 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9226
hERG inhibition (predictor II)Non-inhibitor0.6145
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
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-0329000000-18907cc9c391c98b3b37

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
S100 protein binding
Specific Function
pH-dependent, voltage-insensitive, background potassium channel protein. Rectification direction results from potassium ion concentration on either side of the membrane. Acts as an outward rectifie...
Gene Name
KCNK3
Uniprot ID
O14649
Uniprot Name
Potassium channel subfamily K member 3
Molecular Weight
43517.665 Da
References
  1. Yost CS: A new look at the respiratory stimulant doxapram. CNS Drug Rev. 2006 Fall-Winter;12(3-4):236-49. [Article]
  2. Anderson-Beck R, Wilson L, Brazier S, Hughes IE, Peers C: Doxapram stimulates dopamine release from the intact rat carotid body in vitro. Neurosci Lett. 1995 Feb 24;187(1):25-8. [Article]
  3. Peers C: Effects of doxapram on ionic currents recorded in isolated type I cells of the neonatal rat carotid body. Brain Res. 1991 Dec 24;568(1-2):116-22. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated potassium channel activity
Specific Function
pH-dependent, voltage-insensitive, background potassium channel protein.
Gene Name
KCNK9
Uniprot ID
Q9NPC2
Uniprot Name
Potassium channel subfamily K member 9
Molecular Weight
42263.485 Da
References
  1. Yost CS: A new look at the respiratory stimulant doxapram. CNS Drug Rev. 2006 Fall-Winter;12(3-4):236-49. [Article]
  2. Anderson-Beck R, Wilson L, Brazier S, Hughes IE, Peers C: Doxapram stimulates dopamine release from the intact rat carotid body in vitro. Neurosci Lett. 1995 Feb 24;187(1):25-8. [Article]
  3. Peers C: Effects of doxapram on ionic currents recorded in isolated type I cells of the neonatal rat carotid body. Brain Res. 1991 Dec 24;568(1-2):116-22. [Article]

Drug created at June 13, 2005 13:24 / Updated at August 07, 2021 00:38