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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
DoxapramFrench/German/SpanishINN
DoxapramumLatinINN
Salts
Name/CAS Structure Properties
Doxapram Hydrochloride
Thumb
  • InChI Key: ZOMBFZRWMLIDPX-UHFFFAOYNA-N
  • Monoisotopic Mass: 432.217970639
  • Average Mass: 432.983
DBSALT000643
Brand names
NameCompany
CaropramKhandelwal
Dai Er SongBosen Bio Pharmaceutical
DopramBaxter
Jia Su LunNhwa
StimulexNot Available
Ze LunJiuxu Pharmaceutical
Brand mixturesNot Available
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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassDiphenylmethanes
Direct parentDiphenylmethanes
Alternative parentsPhenylpyrrolidines; Morpholines; Pyrrolidones; Pyrroles; Tertiary Carboxylic Acid Amides; Tertiary Amines; Lactams; Polyamines; Ethers; Carboxylic Acids
Substituents3-phenylpyrrolidine; morpholine; pyrrolidone; oxazinane; pyrrolidine; tertiary carboxylic acid amide; pyrrole; tertiary amine; lactam; carboxamide group; carboxylic acid derivative; polyamine; carboxylic acid; ether; amine; organonitrogen compound
Classification descriptionThis compound belongs to the diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
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
Metabolism
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
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9877
Caco-2 permeable + 0.6673
P-glycoprotein substrate Substrate 0.7033
P-glycoprotein inhibitor I Inhibitor 0.8564
P-glycoprotein inhibitor II Non-inhibitor 0.7037
Renal organic cation transporter Non-inhibitor 0.5199
CYP450 2C9 substrate Non-substrate 0.7735
CYP450 2D6 substrate Non-substrate 0.7295
CYP450 3A4 substrate Substrate 0.6409
CYP450 1A2 substrate Non-inhibitor 0.6917
CYP450 2C9 substrate Non-inhibitor 0.8071
CYP450 2D6 substrate Non-inhibitor 0.7945
CYP450 2C19 substrate Non-inhibitor 0.7838
CYP450 3A4 substrate Non-inhibitor 0.5697
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7109
Ames test Non AMES toxic 0.8198
Carcinogenicity Non-carcinogens 0.8969
Biodegradation Not ready biodegradable 0.9931
Rat acute toxicity 3.1933 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9226
hERG inhibition (predictor II) Non-inhibitor 0.6145
Pharmacoeconomics
Manufacturers
  • Baxter healthcare corp anesthesia and critical care
  • Bedford laboratories div ben venue laboratories inc
  • Watson laboratories inc
Packagers
Dosage forms
FormRouteStrength
Injection, solutionIntravenous
Prices
Unit descriptionCostUnit
Doxapram hcl 20 mg/ml vial4.67USDml
Dopram 20 mg/ml vial2.52USDml
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 solubility3.43e-02 g/lALOGPS
logP3.65ALOGPS
logP3.23ChemAxon
logS-4ALOGPS
pKa (strongest basic)7.23ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count0ChemAxon
polar surface area32.78ChemAxon
rotatable bond count6ChemAxon
refractivity112.85ChemAxon
polarizability43.02ChemAxon
number of rings4ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleYesChemAxon
Spectra
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
ResourceLink
KEGG DrugD01872
PubChem Compound3156
PubChem Substance46506829
ChemSpider3044
ChEBI681848
ChEMBLCHEMBL1754
Therapeutic Targets DatabaseDAP001295
PharmGKBPA164784026
Drug Product Database1914154
RxListhttp://www.rxlist.com/cgi/generic2/doxapram.htm
Drugs.comhttp://www.drugs.com/cdi/doxapram.html
WikipediaDoxapram
ATC CodesR07AB01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelshow(224 KB)
MSDSshow(50.7 KB)
Interactions
Drug InteractionsNot Available
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