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Identification
NameDoxapram
Accession NumberDB00561  (APRD00935)
TypeSmall Molecule
GroupsApproved, Vet Approved
DescriptionA central respiratory stimulant with a brief duration of action. (From Martindale, The Extra Pharmocopoeia, 30th ed, p1225)
Structure
Thumb
Synonyms
(+-)-Doxapram
1-Ethyl-4-(2-morpholinoethyl)-3,3-diphenyl-2-pyrrolidinone
Doxapram
Doxapramum
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Dopraminjection20 mg/mLintravenousWest Ward Pharmaceutical Corp.1965-06-23Not applicableUs
Dopram Inj 20mg/mlliquid20 mgintravenousAyerst Laboratories1992-12-311996-09-10Canada
Dopram Injectable Liq 20mg/mlliquid20 mgintravenousWyeth Ayerst Canada Inc.1994-12-312001-04-23Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not 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
Categories
UNII94F3830Q73
CAS number309-29-5
WeightAverage: 378.5072
Monoisotopic: 378.230728214
Chemical FormulaC24H30N2O2
InChI KeyInChIKey=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
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.
Related Articles
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 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 )
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
Liquidintravenous20 mg
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
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot 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 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. [PubMed:8251281 ]
  2. Yost CS: A new look at the respiratory stimulant doxapram. CNS Drug Rev. 2006 Fall-Winter;12(3-4):236-49. [PubMed:17227289 ]
External Links
ATC CodesR07AB01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (224 KB)
MSDSDownload (50.7 KB)
Interactions
Drug Interactions
Drug
7,8-DICHLORO-1,2,3,4-TETRAHYDROISOQUINOLINE7,8-DICHLORO-1,2,3,4-TETRAHYDROISOQUINOLINE may increase the hypertensive activities of Doxapram.
BenmoxinBenmoxin may increase the hypertensive activities of Doxapram.
CaroxazoneCaroxazone may increase the hypertensive activities of Doxapram.
FurazolidoneFurazolidone may increase the hypertensive activities of Doxapram.
HydracarbazineHydracarbazine may increase the hypertensive activities of Doxapram.
IproclozideIproclozide may increase the hypertensive activities of Doxapram.
IproniazidIproniazid may increase the hypertensive activities of Doxapram.
IsocarboxazidIsocarboxazid may increase the hypertensive activities of Doxapram.
MebanazineMebanazine may increase the hypertensive activities of Doxapram.
Methylene blueMethylene blue may increase the hypertensive activities of Doxapram.
MinaprineMinaprine may increase the hypertensive activities of Doxapram.
MoclobemideMoclobemide may increase the hypertensive activities of Doxapram.
NialamideNialamide may increase the hypertensive activities of Doxapram.
OctamoxinOctamoxin may increase the hypertensive activities of Doxapram.
PargylinePargyline may increase the hypertensive activities of Doxapram.
PhenelzinePhenelzine may increase the hypertensive activities of Doxapram.
PheniprazinePheniprazine may increase the hypertensive activities of Doxapram.
PhenoxypropazinePhenoxypropazine may increase the hypertensive activities of Doxapram.
PirlindolePirlindole may increase the hypertensive activities of Doxapram.
PivhydrazinePivhydrazine may increase the hypertensive activities of Doxapram.
RasagilineRasagiline may increase the hypertensive activities of Doxapram.
SafrazineSafrazine may increase the hypertensive activities of Doxapram.
SelegilineSelegiline may increase the hypertensive activities of Doxapram.
ToloxatoneToloxatone may increase the hypertensive activities of Doxapram.
Trans-2-PhenylcyclopropylamineTrans-2-Phenylcyclopropylamine may increase the hypertensive activities of Doxapram.
TranylcypromineTranylcypromine may increase the hypertensive activities of Doxapram.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
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 rectifier when external potassium concentration is low. When external potassium concentration is high, current is inward.
Gene Name:
KCNK3
Uniprot ID:
O14649
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. [PubMed:17227289 ]
  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:7617294 ]
  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:1667613 ]
Kind
Protein
Organism
Human
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
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. [PubMed:17227289 ]
  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:7617294 ]
  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:1667613 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23