Identification

Name
Droperidol
Accession Number
DB00450  (APRD00939)
Type
Small Molecule
Groups
Approved, Vet approved
Description

A butyrophenone with general properties similar to those of haloperidol. It is used in conjunction with an opioid analgesic such as fentanyl to maintain the patient in a calm state of neuroleptanalgesia with indifference to surroundings but still able to cooperate with the surgeon. It is also used as a premedicant, as an antiemetic, and for the control of agitation in acute psychoses. (From Martindale, The Extra Pharmacopoeia, 29th ed, p593)

Structure
Thumb
Synonyms
  • 1-(1-(3-(P-Fluorobenzoyl)propyl)-1,2,3,6-tetrahydro-4-pyridyl)-2-benzimidazolinone
  • 1-(1-(4-(P-Fluorophenyl)-4-oxobutyl)-1,2,3,6-tetrahydro-4-pyridyl)-2-benzimidazolinone
  • 1-{1-[4-(4-fluoro-phenyl)-4-oxo-butyl]-1,2,3,6-tetrahydro-pyridin-4-yl}-1,3-dihydro-benzoimidazol-2-one
  • 1-{1-[4-(4-fluorophenyl)-4-oxobutyl]-1,2,3,6-tetrahydro-4-pyridinyl}-2,3-dihydro-1H-benzo[D]imidazol-2-one
  • Droperidol
  • Dropéridol
  • Droperidolo
  • Droperidolum
External IDs
McN-JR 4749 / MCN-JR-4749 / R 4749 / R-4749
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Droperidol InjectionLiquid2.5 mgIntramuscular; IntravenousNovopharm Limited1998-04-202002-03-14Canada
Droperidol Injection USP 2.5mg/mlSolution2.5 mgIntramuscular; IntravenousSandoz Canada Incorporated1995-12-31Not applicableCanada
InapsineInjection2.5 mg/1mLIntramuscular; IntravenousTaylor Pharmaceuticals2007-08-09Not applicableUs
InapsineInjection2.5 mg/1mLIntramuscular; IntravenousAkorn1996-07-012012-01-01Us
InapsineInjection2.5 mg/1mLIntramuscular; IntravenousTaylor Pharmaceuticals2007-08-09Not applicableUs
InapsineInjection2.5 mg/1mLIntramuscular; IntravenousAkorn1996-07-012012-01-01Us
Inapsine Inj 2.5mg/mlLiquid2.5 mgIntramuscular; IntravenousJanssen Pharmaceutica, Division Of Janssen Ortho Inc.1982-12-311998-08-10Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DroperidolInjection, solution2.5 mg/1mLIntramuscular; IntravenousAMERICAN REGENT, INC.1990-09-30Not applicableUs
DroperidolInjection, solution2.5 mg/1mLIntramuscular; IntravenousPhysicians Total Care, Inc.1988-02-292002-06-30Us
DroperidolInjection, solution2.5 mg/1mLIntramuscular; IntravenousCardinal Health1990-09-302014-08-31Us
DroperidolInjection, solution2.5 mg/1mLIntramuscular; IntravenousHospira, Inc.2005-08-23Not applicableUs
DroperidolInjection, solution2.5 mg/1mLIntramuscular; IntravenousGeneral Injectables & Vaccines2012-10-182014-07-01Us
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Innovar InjDroperidol (2.5 mg) + Fentanyl citrate (.05 mg)LiquidIntramuscular; IntravenousJanssen Pharmaceutica, Division Of Janssen Ortho Inc.1982-12-311996-09-10Canada
International/Other Brands
Dehydrobenzperidol (Janssen) / Dridol (Prostrakan) / Droleptan (Daiichi Sankyo) / Dropedol (Excelsior) / Dropel (Siu Guan) / Droperdal (Cristália) / Droperidols (Grindeks) / Xomolix (Arzneimittel ProStrakan)
Categories
UNII
O9U0F09D5X
CAS number
548-73-2
Weight
Average: 379.4274
Monoisotopic: 379.169605168
Chemical Formula
C22H22FN3O2
InChI Key
RMEDXOLNCUSCGS-UHFFFAOYSA-N
InChI
InChI=1S/C22H22FN3O2/c23-17-9-7-16(8-10-17)21(27)6-3-13-25-14-11-18(12-15-25)26-20-5-2-1-4-19(20)24-22(26)28/h1-2,4-5,7-11H,3,6,12-15H2,(H,24,28)
IUPAC Name
1-{1-[4-(4-fluorophenyl)-4-oxobutyl]-1,2,3,6-tetrahydropyridin-4-yl}-2,3-dihydro-1H-1,3-benzodiazol-2-one
SMILES
FC1=CC=C(C=C1)C(=O)CCCN1CCC(=CC1)N1C(=O)NC2=CC=CC=C12

Pharmacology

Indication

Droperidol is ssed to produce tranquilization and to reduce the incidence of nausea and vomiting in surgical and diagnostic procedures.

Associated Conditions
Associated Therapies
Pharmacodynamics

Droperidol produces marked tranquilization and sedation. It allays apprehension and provides a state of mental detachment and indifference while maintaining a state of reflex alertness. Droperidol produces an antiemetic effect as evidenced by the antagonism of apomorphine in dogs. It lowers the incidence of nausea and vomiting during surgical procedures and provides antiemetic protection in the postoperative period. Droperidol potentiates other CNS depressants. It produces mild alpha-adrenergic blockade, peripheral vascular dilatation and reduction of the pressor effect of epinephrine. It can produce hypotension and decreased peripheral vascular resistance and may decrease pulmonary arterial pressure (particularly if it is abnormally high). It may reduce the incidence of epinephrine-induced arrhythmias, but it does not prevent other cardiac arrhythmias.

Mechanism of action

The exact mechanism of action is unknown, however, droperidol causes a CNS depression at subcortical levels of the brain, midbrain, and brainstem reticular formation. It may antagonize the actions of glutamic acid within the extrapyramidal system. It may also inhibit cathecolamine receptors and the reuptake of neurotransmiters and has strong central antidopaminergic action and weak central anticholinergic action. It can also produce ganglionic blockade and reduced affective response. The main actions seem to stem from its potent Dopamine(2) receptor antagonism with minor antagonistic effects on alpha-1 adrenergic receptors as well.

TargetActionsOrganism
AD(2) dopamine receptor
antagonist
Human
AAlpha-1A adrenergic receptor
antagonist
Human
Absorption

Completely absorbed following intramuscular administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Extensively metabolized.

Route of elimination
Not Available
Half life

Biphasic distribution. The rapid distribution phase is 1.4 ± 0.5 minutes and the slower distribution phase is 14.3 ± 6.5 minutes. Elimination half-life in adults is 134 ± 13 minutes and may be increased in geriatric patients. In children, it is 101.5 ± 26.4 minutes.

Clearance
Not Available
Toxicity

The intravenous LD50 of droperidol is 20-43 mg/kg in mice; 30 mg/kg in rats; 25 mg/kg in dogs and 11-13 mg/kg in rabbits. The intramuscular LD50 of droperidol is 195 mg/kg in mice, 104-110 mg/kg in rats; 97 mg/kg in rabbits and 200 mg/kg in guinea pigs. The manifestations of droperidol overdosage are an extension of its pharmacologic actions.

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

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamineDroperidol may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineDroperidol may increase the central nervous system depressant (CNS depressant) activities of 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineDroperidol may increase the central nervous system depressant (CNS depressant) activities of 3,4-Methylenedioxyamphetamine.
3,5-DinitrocatecholThe therapeutic efficacy of 3,5-Dinitrocatechol can be decreased when used in combination with Droperidol.
4-Bromo-2,5-dimethoxyamphetamineDroperidol may increase the central nervous system depressant (CNS depressant) activities of 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineDroperidol may increase the central nervous system depressant (CNS depressant) activities of 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineDroperidol may increase the central nervous system depressant (CNS depressant) activities of 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleDroperidol may increase the central nervous system depressant (CNS depressant) activities of 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineDroperidol may increase the central nervous system depressant (CNS depressant) activities of 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
AbediterolThe therapeutic efficacy of Abediterol can be decreased when used in combination with Droperidol.
Food Interactions
Not Available

References

Synthesis Reference

Janssen, P.A.J. and Gardocki, J.F.; U.S. Patent 3,141,823; July 21, 1964; assigned to Research Laboratorium Dr. C. Janssen NV, Belgium. Januen, P.A.J.; U.S. Patent 3,161,645; December 15,1964: assigned to Research Laboratorium Dr. C. Janssen NV, Belgium.

US3161645
General References
Not Available
External Links
Human Metabolome Database
HMDB0014593
KEGG Drug
D00308
PubChem Compound
3168
PubChem Substance
46505291
ChemSpider
3056
BindingDB
50017705
ChEBI
4717
ChEMBL
CHEMBL1108
Therapeutic Targets Database
DAP000412
PharmGKB
PA449422
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Droperidol
ATC Codes
N05AD08 — Droperidol
AHFS Codes
  • 28:24.92 — Miscellaneous Anxiolytics Sedatives and Hypnotics
MSDS
Download (74 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedPreventionPost-Operative Nausea and Vomiting (PONV) / Postoperative Emesis1
3CompletedTreatmentInteraction Between Antiemetic Drugs and Paracetamol1
3CompletedTreatmentPain NOS1
3Unknown StatusTreatmentPsychosis Nos/Other1
4CompletedPreventionCardiac Repolarization1
4CompletedPreventionPost-Operative Nausea and Vomiting (PONV)1
4CompletedPreventionVomiting1
4RecruitingTreatmentHallux Valgus1
4RecruitingTreatmentInguinal Hernias / Postoperative pain1
4TerminatedPreventionNausea / Vomiting1
4Unknown StatusTreatmentCholecystolithiasis1
Not AvailableCompletedNot AvailableSchizophrenic Disorders1
Not AvailableCompletedPreventionPost-Operative Nausea and Vomiting (PONV)2
Not AvailableCompletedTreatmentMyocardial Repolarization1
Not AvailableNot Yet RecruitingTreatmentGeneral Surgery / Hallux Valgus1
Not AvailableTerminatedTreatmentPrimary Headaches (Includes Migraines, Tension, Cluster Headaches)1

Pharmacoeconomics

Manufacturers
  • Abraxis pharmaceutical products
  • Astrazeneca lp
  • Hospira inc
  • Luitpold pharmaceuticals inc
  • Smith and nephew solopak div smith and nephew
  • Solopak laboratories inc
  • Watson laboratories inc
  • Akorn inc
Packagers
  • Akorn Inc.
  • American Regent
  • Cardinal Health
  • Hospira Inc.
  • Luitpold Pharmaceuticals Inc.
  • Neuman Distributors Inc.
  • Physicians Total Care Inc.
  • Taylor Pharmaceuticals
Dosage forms
FormRouteStrength
Injection, solutionIntramuscular; Intravenous2.5 mg/1mL
SolutionIntramuscular; Intravenous2.5 mg
InjectionIntramuscular; Intravenous2.5 mg/1mL
LiquidIntramuscular; Intravenous2.5 mg
LiquidIntramuscular; Intravenous
Prices
Unit descriptionCostUnit
Inapsine 2.5 mg/ml ampul4.59USD ml
Droperidol 2.5 mg/ml vial2.04USD ml
Droperidol 2.5 mg/ml ampul0.7USD 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)145-146.5Janssen, P.A.J. and Gardocki, J.F.; U.S. Patent 3,141,823; July 21, 1964; assigned to Research Laboratorium Dr. C. Janssen NV, Belgium. Januen, P.A.J.; U.S. Patent 3,161,645; December 15,1964: assigned to Research Laboratorium Dr. C. Janssen NV, Belgium.
water solubility4.21 mg/LNot Available
logP3.50SANGSTER (1993)
pKa7.46SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.0966 mg/mLALOGPS
logP3.93ALOGPS
logP3.01ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)12.72ChemAxon
pKa (Strongest Basic)6.75ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area52.65 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity109.52 m3·mol-1ChemAxon
Polarizability40.31 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9602
Caco-2 permeable-0.7521
P-glycoprotein substrateSubstrate0.7471
P-glycoprotein inhibitor IInhibitor0.9128
P-glycoprotein inhibitor IIInhibitor0.7451
Renal organic cation transporterInhibitor0.67
CYP450 2C9 substrateNon-substrate0.7884
CYP450 2D6 substrateNon-substrate0.8756
CYP450 3A4 substrateSubstrate0.6751
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorInhibitor0.796
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9279
Ames testNon AMES toxic0.6353
CarcinogenicityNon-carcinogens0.9104
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5820 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.8955
hERG inhibition (predictor II)Inhibitor0.835
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
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-001i-0209000000-83800a9c755f8223f328
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0006-0900000000-418e20f120e395aac71a
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-014i-0900000000-2888306b46b834e3dd3b
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-014i-0900000000-0cff909ec834cc05a2d3
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00xr-0900000000-f910b21f009854002b17
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001l-0609000000-b071b906d4d1f94ae833
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00kf-0900000000-ac3d815681b1b57a53b5
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0900000000-b2c3fb5ea6889dbf960c
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00xr-0900000000-01bdbb9758cd0acb8864
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00di-0900000000-09ecdeee9f023e5ac679
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00di-0900000000-be69940105e80f5ab869
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00di-2900000000-9a55a536e908d6236924
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00fr-9800000000-4462513b0f99ffd6ce93
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00b9-9200000000-b61d87593ee28d4b283e
MS/MS Spectrum - , positiveLC-MS/MSsplash10-001i-0918000000-1efb9a7c97db08bb65d2
MS/MS Spectrum - , positiveLC-MS/MSsplash10-014i-2900000000-dd5f00934e38a7c6ddbb

Taxonomy

Description
This compound belongs to the class of organic compounds known as alkyl-phenylketones. These are aromatic compounds containing a ketone substituted by one alkyl group, and a phenyl group.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbonyl compounds
Direct Parent
Alkyl-phenylketones
Alternative Parents
Phenylbutylamines / Butyrophenones / Benzimidazoles / Aryl alkyl ketones / Benzoyl derivatives / Fluorobenzenes / Aryl fluorides / N-substituted imidazoles / Hydropyridines / Gamma-amino ketones
show 8 more
Substituents
Alkyl-phenylketone / Phenylbutylamine / Butyrophenone / Benzimidazole / Benzoyl / Aryl alkyl ketone / Halobenzene / Fluorobenzene / Aryl fluoride / Aryl halide
show 22 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organofluorine compound, aromatic ketone, benzimidazoles (CHEBI:4717)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Potassium channel regulator activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name
DRD2
Uniprot ID
P14416
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
References
  1. Grip G, Svensson BA, Gordh T Jr, Post C, Hartvig P: Histopathology and evaluation of potentiation of morphine-induced antinociception by intrathecal droperidol in the rat. Acta Anaesthesiol Scand. 1992 Feb;36(2):145-52. [PubMed:1549935]
  2. Hamik A, Peroutka SJ: Differential interactions of traditional and novel antiemetics with dopamine D2 and 5-hydroxytryptamine3 receptors. Cancer Chemother Pharmacol. 1989;24(5):307-10. [PubMed:2527092]
  3. Larson MD: The effect of antiemetics on pupillary reflex dilation during epidural/general anesthesia. Anesth Analg. 2003 Dec;97(6):1652-6. [PubMed:14633536]
  4. Gao HR, Shi TF, Yang CX, Zhang D, Zhang GW, Zhang Y, Jiao RS, Zhang H, Xu MY: The effect of dopamine on pain-related neurons in the parafascicular nucleus of rats. J Neural Transm (Vienna). 2010 May;117(5):585-91. doi: 10.1007/s00702-010-0398-3. Epub 2010 Apr 1. [PubMed:20358234]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. Zupko I, Janossy K, Maul K, Marki A, Falkay G: Alpha-adrenergic blockade: a possible mechanism of tocolytic action of certain benzodiazepines in a postpartum rat model in vivo. Life Sci. 2003 Jan 24;72(10):1093-102. [PubMed:12505540]

Drug created on June 13, 2005 07:24 / Updated on November 13, 2018 07:48