Identification

Name
Doxapram
Accession Number
DB00561  (APRD00935)
Type
Small Molecule
Groups
Approved, Vet Approved
Description

A 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
Product Ingredients
IngredientUNIICASInChI Key
Doxapram HydrochlorideP5RU6UOQ5Y7081-53-0ZOMBFZRWMLIDPX-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DopramInjection20 mg/mLIntravenousWest Ward Pharmaceutical1965-06-23Not 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
International/Other Brands
Caropram (Khandelwal) / Dai Er Song (Bosen Bio Pharmaceutical) / Jia Su Lun (Nhwa) / Stimulex / Ze Lun (Jiuxu Pharmaceutical)
Categories
UNII
94F3830Q73
CAS number
309-29-5
Weight
Average: 378.5072
Monoisotopic: 378.230728214
Chemical Formula
C24H30N2O2
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

Pharmacology

Indication

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

Structured Indications
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
Human
APotassium channel subfamily K member 9
inhibitor
Human
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
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.

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

Interactions

Drug Interactions
DrugInteractionDrug group
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypertensive activities of Doxapram.Experimental
AmphetamineAmphetamine may increase the hypertensive activities of Doxapram.Approved, Illicit
BenmoxinBenmoxin may increase the hypertensive activities of Doxapram.Withdrawn
BrofaromineBrofaromine may increase the hypertensive activities of Doxapram.Experimental
CaroxazoneCaroxazone may increase the hypertensive activities of Doxapram.Withdrawn
FurazolidoneFurazolidone may increase the hypertensive activities of Doxapram.Approved, Investigational, Vet Approved
HarmalineHarmaline may increase the hypertensive activities of Doxapram.Experimental
HydracarbazineHydracarbazine may increase the hypertensive activities of Doxapram.Experimental
IproclozideIproclozide may increase the hypertensive activities of Doxapram.Withdrawn
IproniazidIproniazid may increase the hypertensive activities of Doxapram.Withdrawn
IsocarboxazidIsocarboxazid may increase the hypertensive activities of Doxapram.Approved
MebanazineMebanazine may increase the hypertensive activities of Doxapram.Withdrawn
Methylene blueMethylene blue may increase the hypertensive activities of Doxapram.Approved, Investigational
MinaprineMinaprine may increase the hypertensive activities of Doxapram.Approved
MoclobemideMoclobemide may increase the hypertensive activities of Doxapram.Approved
NialamideNialamide may increase the hypertensive activities of Doxapram.Withdrawn
OctamoxinOctamoxin may increase the hypertensive activities of Doxapram.Withdrawn
PargylinePargyline may increase the hypertensive activities of Doxapram.Approved
PhenelzinePhenelzine may increase the hypertensive activities of Doxapram.Approved
PheniprazinePheniprazine may increase the hypertensive activities of Doxapram.Withdrawn
PhenoxypropazinePhenoxypropazine may increase the hypertensive activities of Doxapram.Withdrawn
PirlindolePirlindole may increase the hypertensive activities of Doxapram.Approved
PivhydrazinePivhydrazine may increase the hypertensive activities of Doxapram.Withdrawn
ProcarbazineProcarbazine may increase the hypertensive activities of Doxapram.Approved
RasagilineRasagiline may increase the hypertensive activities of Doxapram.Approved
SafrazineSafrazine may increase the hypertensive activities of Doxapram.Withdrawn
SelegilineSelegiline may increase the hypertensive activities of Doxapram.Approved, Investigational, Vet Approved
ToloxatoneToloxatone may increase the hypertensive activities of Doxapram.Approved
Trans-2-PhenylcyclopropylamineTrans-2-Phenylcyclopropylamine may increase the hypertensive activities of Doxapram.Experimental
TranylcypromineTranylcypromine may increase the hypertensive activities of Doxapram.Approved
Food Interactions
Not 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
Human Metabolome Database
HMDB14701
KEGG Drug
D01872
PubChem Compound
3156
PubChem Substance
46506829
ChemSpider
3044
ChEBI
681848
ChEMBL
CHEMBL1754
Therapeutic Targets Database
DAP001295
PharmGKB
PA164784026
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Doxapram
ATC Codes
R07AB01 — Doxapram
FDA label
Download (224 KB)
MSDS
Download (50.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentAnaesthesia1
2CompletedTreatmentPanic Attacks / Treatment of Induced Panic Attack1
4CompletedSupportive CareArterial hypoxia / Sedation therapy1
4CompletedTreatmentApnea / Infants, Premature1
Not AvailableActive Not RecruitingTreatmentAnaesthesia therapy1

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.
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

Taxonomy

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
Diphenylmethane / 3-phenylpyrrolidine / Aralkylamine / Morpholine / Oxazinane / Pyrrolidone / 2-pyrrolidone / N-alkylpyrrolidine / Pyrrole / Pyrrolidine
show 22 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
morpholines, pyrrolidin-2-ones (CHEBI:681848)

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 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. [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
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. [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]

Drug created on June 13, 2005 07:24 / Updated on December 01, 2017 17:15