DROPERIDOL

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H22FN3O2
Molecular Weight	379.4274
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

FC1=CC=C(C=C1)C(=O)CCCN2CCC(=CC2)N3C(=O)NC4=CC=CC=C34

InChI

InChIKey=RMEDXOLNCUSCGS-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C22H22FN3O2
Molecular Weight	379.4274
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.drugbank.ca/drugs/DB00450
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/pro/droperidol.html

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

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Dopamine D2 receptor 297 Target ID: CHEMBL217 Sources: http://www.drugbank.ca/drugs/DB00450	Antagonist 2778
Alpha-1a adrenergic receptor 66 Target ID: CHEMBL229 Sources: http://www.drugbank.ca/drugs/DB00450	Antagonist 2778
HERG 92 Target ID: CHEMBL240 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12190308	Inhibitor 8297	32.2 nM [IC50]
Serotonin 2a (5-HT2a) receptor 231 Target ID: CHEMBL224 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2879412	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Nausea and vomiting associated with surgical and diagnostic procedures 2 Sources: https://www.drugs.com/pro/droperidol.html	Secondary		Approved 8429	INAPSINE Approved Use Droperidol injection is indicated to reduce the incidence of nausea and vomiting associated with surgical and diagnostic procedures. Launch Date 1970

C_max

Value	Dose	Co-administered	Analyte	Population
6.5 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30574300/	0.02 mg/kg single, nasal dose: 0.02 mg/kg route of administration: Nasal experiment type: SINGLE co-administered:		DROPERIDOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
26.6 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30574300/	0.02 mg/kg single, intravenous dose: 0.02 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		DROPERIDOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
18.7 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30574300/	0.02 mg/kg single, nasal dose: 0.02 mg/kg route of administration: Nasal experiment type: SINGLE co-administered:		DROPERIDOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
40 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30574300/	0.02 mg/kg single, intravenous dose: 0.02 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		DROPERIDOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30574300/	0.02 mg/kg single, nasal dose: 0.02 mg/kg route of administration: Nasal experiment type: SINGLE co-administered:		DROPERIDOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30574300/	0.02 mg/kg single, intravenous dose: 0.02 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		DROPERIDOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
0.4 mg/kg multiple, oral Dose: 0.4 mg/kg Route: oral Route: multiple Dose: 0.4 mg/kg Sources: https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2044.2009.06124.x https://pubmed.ncbi.nlm.nih.gov/337985	unhealthy, 2-9 years Health Status: unhealthy Age Group: 2-9 years Sources: https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2044.2009.06124.x https://pubmed.ncbi.nlm.nih.gov/337985	Disc. AE: QT interval prolonged... AEs leading to discontinuation/dose reduction: QT interval prolonged Sources: https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2044.2009.06124.x https://pubmed.ncbi.nlm.nih.gov/337985
8.25 mg single, intramuscular Highest studied dose Dose: 8.25 mg Route: intramuscular Route: single Dose: 8.25 mg Sources: https://pubmed.ncbi.nlm.nih.gov/25416184 https://pubmed.ncbi.nlm.nih.gov/12552051	unhealthy, 42 ± 10.0 years n = 61 Health Status: unhealthy Condition: acute migraine headache Age Group: 42 ± 10.0 years Sex: M+F Population Size: 61 Sources: https://pubmed.ncbi.nlm.nih.gov/25416184 https://pubmed.ncbi.nlm.nih.gov/12552051	Other AEs: Asthenia, Chills... Other AEs: Asthenia (24.6%) Chills (3.3%) Anorexia (3.3%) Akathisia (16.4%) Anxiety (27.9%) Confusion (3.3%) Dizziness (9.8%) Dry mouth (9.8%) Nervousness (4.9%) Paresthesia (3.3%) Somnolence (24.6%) Tremor (1.6%) Pharyngitis (4.9%) Rhinitis (4.9%) Sweaty (8.2%) Sources: https://pubmed.ncbi.nlm.nih.gov/25416184 https://pubmed.ncbi.nlm.nih.gov/12552051
2.5 mg multiple, intravenous (starting) Dose: 2.5 mg Route: intravenous Route: multiple Dose: 2.5 mg Sources: https://pubmed.ncbi.nlm.nih.gov/15320756 https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2044.2009.06124.x	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/15320756 https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2044.2009.06124.x	Disc. AE: Torsades de pointes... AEs leading to discontinuation/dose reduction: Torsades de pointes Sources: https://pubmed.ncbi.nlm.nih.gov/15320756 https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2044.2009.06124.x

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MRP1 106	CYP3A5 395

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
MRP1 172	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/dmd/early/2018/09/19/dmd.118.081612.full.pdf Page: 19.0	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1737	substrate 3367 Sources: https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1016/S0009-9236%2803%2990413-9	major
CYP3A5 395	substrate 3367 Sources: https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1016/S0009-9236%2803%2990413-9	major

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/18349188/

Sourcing

Vendor/Aggregator	ID	URL
PubChem	9956314	https://pubchem.ncbi.nlm.nih.gov/compound/9956314
SureChEMBL	SCHEMBL8356614	https://www.surechembl.org/chemical/SCHEMBL8356614
Wikidata	Q27236492

PubMed

Title	Date	PubMed
[Does the addition of an anxiolytic drug improve the anti-emetic effectiveness of the steroid and granisetron combination in the prophylaxis of cisplatin-induced vomiting?].	2001 Aug 5	11556262
[Prophylaxis of nausea and vomiting after thyroid surgery: comparison of oral and intravenous dolasetron with intravenous droperidol and placebo].	2001 Jul	11496617
Neuroleptic malignant syndrome induced by droperidol.	2001 Mar	11406684
Pediatric renal transplantation: anesthesia and perioperative complications.	2001 Mar	11315282
Dexamethasone for preventing nausea and vomiting associated with epidural morphine: a dose-ranging study.	2001 Mar	11226112
[And now we present droperidol!].	2001 May	11419247
Impact of antiemetic selection on postoperative nausea and vomiting and patient satisfaction.	2001 May	11349743
Antipsychotic drugs: prolonged QTc interval, torsade de pointes, and sudden death.	2001 Nov	11691681
IM droperidol as premedication attenuates intraoperative hypothermia.	2001 Oct	11606340
[Postoperative nausea--still a problem].	2001 Oct 3	11685757
A placebo-controlled, randomized trial of droperidol versus metoclopramide for outpatients undergoing gynecological laparoscopy under conscious sedation.	2002 Apr	12118494
Use of sevoflurane during cardiopulmonary bypass decreases incidence of awareness.	2002 Apr	12074418
Droperidol inhibits GABA(A) and neuronal nicotinic receptor activation.	2002 Apr	11964609
A randomized clinical trial to assess the efficacy of intramuscular droperidol for the treatment of acute migraine headache.	2002 Jan	11781912
Effects of sevoflurane on electrocorticography in patients with intractable temporal lobe epilepsy.	2002 Jan	11773826
Droperidol "box warning" warrants scrutiny.	2002 Jul	12131146
Gateways to Clinical Trials. June 2002.	2002 Jun	12168506
Droperidol--behind the black box warning.	2002 Jun	12045077
Rapid tranquillisation: time for a reappraisal of options for parenteral therapy.	2002 Jun	12042225
Oral ondansetron, tropisetron or metoclopramide to prevent postoperative nausea and vomiting: a comparison in high-risk patients undergoing thyroid or parathyroid surgery.	2002 May	12027845
Psychotropic drugs and the ECG: focus on the QTc interval.	2002 May	11996627

Patents

Sample Use Guides

In Vivo Use Guide

Dosage: The dosage should be individualized. Factors to be considered in determining dose are age, body weight, physical status, underlying pathological condition, use of other drugs, the type of anesthesia to be used, and the surgical procedure involved. Vital signs and ECG should be monitored closely. Maximum Dosage: The maximum recommended initial dose is 2.5 mg IM or slow IV. Additional 1.25 mg doses of droperidol may be administered to achieve the desired effect. The additional doses should be administered with caution and only if the potential benefit outweighs the potential risk.

Route of Administration: Intravenous

In Vitro Use Guide

Droperidol (10(-7) M) caused vasodilator effect (approximately 20% of vasorelaxation compared with maximal vasorelaxation induced by papaverine [3 x 10(-4) M] in rat vascular smooth muscle cells.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 16:31:24 GMT 2023` Edited by `admin` on `Sat Dec 16 16:31:24 GMT 2023`
Record UNII	O9U0F09D5X
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DROPERIDOL

Official Name

English

R-4749

Code

English

NSC-169874

Code

English

DROPERIDOL [VANDF]

Common Name

English

DROPERIDOL [ORANGE BOOK]

Common Name

English

MCN-JR-4749

Code

English

DROPERIDOL [GREEN BOOK]

Common Name

English

DROPERIDOL [USP-RS]

Common Name

English

INNOVAR COMPONENT DROPERIDOL

Common Name

English

DROPERIDOL [MART.]

Common Name

English

DROPERIDOL [USP MONOGRAPH]

Common Name

English

Droperidol [WHO-DD]

Common Name

English

1-(1-(3-(P-FLUOROBENZOYL)PROPYL)-1,2,3,6-TETRAHYDRO-4-PYRIDYL)-2-BENZIMIDAZOLINONE

Common Name

English

DROPERIDOL [HSDB]

Common Name

English

DROPERIDOL [USAN]

Common Name

English

DROPERIDOL COMPONENT OF INNOVAR

Common Name

English

DROPERIDOL [JAN]

Common Name

English

2H-BENZIMIDAZOL-2-ONE, 1-(1-(4-(4-FLUOROPHENYL)-4-OXOBUTYL)-1,2,3,6-TETRAHYDRO-4-PYRIDINYL)-1,3-DIHYDRO-

Systematic Name

English

droperidol [INN]

Common Name

English

DROPERIDOL [MI]

Common Name

English

INAPSINE

Brand Name

English

DROPERIDOL [EP MONOGRAPH]

Common Name

English

DROLEPTAN

Brand Name

English

Classification Tree Code System Code

WHO-ATC

N05AD08