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Identification
NameDoxapram
Accession NumberDB00561  (APRD00935)
TypeSmall Molecule
GroupsApproved
Description

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

Structure
Thumb
Synonyms
SynonymLanguageCode
(+-)-DoxapramNot AvailableNot Available
1-Ethyl-4-(2-morpholinoethyl)-3,3-diphenyl-2-pyrrolidinoneNot AvailableNot Available
DoxapramFrench/German/SpanishINN
DoxapramumLatinINN
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Dopraminjection20 mg/mLintravenousWest Ward Pharmaceutical Corp.1965-06-23Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Dopraminjection20 mg/mLintravenousBaxter Healthcare Corporation2010-11-29Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
CaropramKhandelwal
Dai Er SongBosen Bio Pharmaceutical
Jia Su LunNhwa
StimulexNot Available
Ze LunJiuxu Pharmaceutical
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Doxapram Hydrochloride
Thumb
  • InChI Key: ZOMBFZRWMLIDPX-UHFFFAOYNA-N
  • Monoisotopic Mass: 432.217970639
  • Average Mass: 432.983
DBSALT000643
CategoriesNot Available
CAS number309-29-5
WeightAverage: 378.5072
Monoisotopic: 378.230728214
Chemical FormulaC24H30N2O2
InChI KeyXFDJYSQDBULQSI-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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassDiphenylmethanes
Direct ParentDiphenylmethanes
Alternative Parents
Substituents
  • Diphenylmethane
  • 3-phenylpyrrolidine
  • Aralkylamine
  • N-alkylpyrrolidine
  • 2-pyrrolidone
  • Pyrrolidone
  • Oxazinane
  • Morpholine
  • Tertiary carboxylic acid amide
  • Pyrrolidine
  • Pyrrole
  • Tertiary aliphatic amine
  • Tertiary amine
  • Lactam
  • Carboxamide group
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Ether
  • Dialkyl ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor use as a temporary measure in hospitalized patients with acute respiratory insufficiency superimposed on chronic obstructive pulmonary disease.
PharmacodynamicsDoxapram 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 actionDoxapram produces respiratory stimulation mediated through the peripheral carotid chemoreceptors. It is thought to stimulate the carotid body by inhibiting certain potassium channels.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityIntravenous 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.
Affected organisms
  • Humans and other mammals
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+0.9877
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 substrateNon-inhibitor0.8071
CYP450 2D6 substrateNon-inhibitor0.7945
CYP450 2C19 substrateNon-inhibitor0.7838
CYP450 3A4 substrateNon-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
Pharmacoeconomics
Manufacturers
  • Baxter healthcare corp anesthesia and critical care
  • Bedford laboratories div ben venue laboratories inc
  • Watson laboratories inc
Packagers
Dosage forms
FormRouteStrength
Injectionintravenous20 mg/mL
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.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point217-219Lunsford, 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
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
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 Reference
  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. Pubmed
  2. Yost CS: A new look at the respiratory stimulant doxapram. CNS Drug Rev. 2006 Fall-Winter;12(3-4):236-49. Pubmed
External Links
ATC CodesR07AB01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (224 KB)
MSDSDownload (50.7 KB)
Interactions
Drug Interactions
Drug
AcebutololMay enhance the adverse/toxic effect of other Sympathomimetics.
AmphetamineMay enhance the adverse/toxic effect of other Sympathomimetics.
AtomoxetineMay enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics.
BenzphetamineMay enhance the adverse/toxic effect of other Sympathomimetics.
ChlorphentermineMay enhance the adverse/toxic effect of other Sympathomimetics.
ClenbuterolMay enhance the adverse/toxic effect of other Sympathomimetics.
DobutamineMay enhance the adverse/toxic effect of other Sympathomimetics.
DopamineMay enhance the adverse/toxic effect of other Sympathomimetics.
EpinephrineMay enhance the adverse/toxic effect of other Sympathomimetics.
FenoterolMay enhance the adverse/toxic effect of other Sympathomimetics.
FormoterolMay enhance the adverse/toxic effect of other Sympathomimetics.
IsocarboxazidMAO Inhibitors may enhance the hypertensive effect of Doxapram.
IsoprenalineMay enhance the adverse/toxic effect of other Sympathomimetics.
LabetalolMay enhance the adverse/toxic effect of other Sympathomimetics.
LinezolidMay enhance the hypertensive effect of Sympathomimetics.
MephentermineMay enhance the adverse/toxic effect of other Sympathomimetics.
MetaraminolMay enhance the adverse/toxic effect of other Sympathomimetics.
MethamphetamineMay enhance the adverse/toxic effect of other Sympathomimetics.
MethoxamineMay enhance the adverse/toxic effect of other Sympathomimetics.
MidodrineMay enhance the adverse/toxic effect of other Sympathomimetics.
MoclobemideMAO Inhibitors may enhance the hypertensive effect of Doxapram.
NaphazolineMay enhance the adverse/toxic effect of other Sympathomimetics.
NorepinephrineMay enhance the adverse/toxic effect of other Sympathomimetics.
OrciprenalineMay enhance the adverse/toxic effect of other Sympathomimetics.
OxymetazolineMay enhance the adverse/toxic effect of other Sympathomimetics.
PhenelzineMAO Inhibitors may enhance the hypertensive effect of Doxapram.
PhenmetrazineMay enhance the adverse/toxic effect of other Sympathomimetics.
PhentermineMay enhance the adverse/toxic effect of other Sympathomimetics.
PhenylephrineMay enhance the adverse/toxic effect of other Sympathomimetics.
PhenylpropanolamineMay enhance the adverse/toxic effect of other Sympathomimetics.
ProcarbazineMAO Inhibitors may enhance the hypertensive effect of Doxapram.
RasagilineMAO Inhibitors may enhance the hypertensive effect of Doxapram.
RitodrineMay enhance the adverse/toxic effect of other Sympathomimetics.
SalmeterolMay enhance the adverse/toxic effect of other Sympathomimetics.
SelegilineMAO Inhibitors may enhance the hypertensive effect of Doxapram.
TerbutalineMay enhance the adverse/toxic effect of other Sympathomimetics.
TranylcypromineMAO Inhibitors may enhance the hypertensive effect of Doxapram.
Food InteractionsNot Available

Targets

1. Potassium channel subfamily K member 3

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Potassium channel subfamily K member 3 O14649 Details

References:

  1. Yost CS: A new look at the respiratory stimulant doxapram. CNS Drug Rev. 2006 Fall-Winter;12(3-4):236-49. Pubmed
  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. Pubmed
  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. Pubmed

2. Potassium channel subfamily K member 9

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Potassium channel subfamily K member 9 Q9NPC2 Details

References:

  1. Yost CS: A new look at the respiratory stimulant doxapram. CNS Drug Rev. 2006 Fall-Winter;12(3-4):236-49. Pubmed
  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. Pubmed
  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. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on April 15, 2014 15:07