Droperidol causes peripheral vascular dilatation and mild α-adrenergic blockade. Droperidol has been shown to block potassium efflux in the myocardium in isolated animal ventricular myocytes, resulting in a dose-dependent delay in repolarization. In isolated animal Purkinje fibers, droperidol has also been demonstrated to cause early depolarizations. [1]

Droperidol (0.01 mM-0.3 mM) increases the action potential duration (APD) in a dose-dependent manner while leaving the other parameters unchanged in rabbit Purkinje fibers stimulated at 60 pulses/min. In rabbit Purkinje fibers, droperidol (1 mM–3 mM) causes the prolonging effect to reverse. In rabbit Purkinje fibers, droperidol (10 mM–30 mM) causes a considerable reduction in Vmax, action potential amplitude, and resting membrane potential in addition to a 50% repolarization in APD shortening. Droperidol has a dual effect on rabbit Purkinje fiber repolarization, prolongation at low concentrations with EAD development, and subsequent triggered activity.[2] Droperidol (3 mg/kg, single dose) reduces the apomorphine effects of rats as well as their locomotion and rearing frequencies in an open field in a dose-dependent manner. Rats given droperidol (3 mg/kg) over an extended period of time develop a notable tolerance to all activity parameters observed in the open environment. Withdrawing from droperidol increases reactivity to apomorphine-induced stereotyped behavior.[3]

Absorption, Distribution and Excretion
Completely absorbed following intramuscular administration.
Following im or iv administration, the onset of pharmacologic action of droperidol occurs within 3-10 minutes, but peak pharmacologic effects may not be apparent until 30 minutes. The sedative and tranquilizing effects of droperidol generally persist for 2-4 hours following im or iv administration of a single dose; alteration of consciousness may persist for up to 12 hours.
Droperidol reportedly crosses the blood-brain barrier and is distributed into the CSF.
Droperidol drug reportedly crosses the placenta, but data are limited.
It is not known if droperidol is distributed into milk.
For more Absorption, Distribution and Excretion (Complete) data for DROPERIDOL (7 total), please visit the HSDB record page.

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Metabolism / Metabolites
Extensively metabolized.
Although the exact metabolic fate of droperidol is not clearly established, the drug is metabolized in the liver. The butyrophenone moiety of droperidol is metabolized to p-fluorophenylacetic acid, which is then conjugated with glycine. The nitrogenous moiety of droperidol appears to be metabolized to benzimidazolone and p-hydroxypiperidine.

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Biological 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.
...Droperidol is rapidly absorbed after im injections, and plasma-level profiles of unchanged drug obey 2-compartment model kinetics. Plasma t1/2 is about 130 min...

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Because little information is available on the long-term use of droperidol during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. Single-dose or short-term use during breastfeeding, such as during surgery, is unlikely to adversely affect the breastfed infant, especially if the infant is older than 2 months. When multiple doses are given to the mother, monitor the infant for drowsiness, especially in younger, exclusively breastfed infants and when using combinations of psychotropic drugs.
◉ Effects in Breastfed Infants
A randomized study compared the breastfed infants born by cesarean section whose mothers received either morphine or morphine plus droperidol by patient-controlled analgesia postoperatively. On days 1 and 2 of life, the infants whose mothers received droperidol had a lower neonatal neurologic and adaptive capacity score (NACS) than those who received morphine only.
One breastfed (extent not stated) infant whose mother was taking droperidol had a somewhat decreased intellectual development on testing, but her mother had also taken olanzapine, clonazepam, sertraline, thioridazine and valproic acid while breastfeeding.
◉ Effects on Lactation and Breastmilk
Hyperprolactinemia has been reported in patients taking long-term droperidol and after short-term use during surgical procedures. The maternal prolactin level in a mother with established lactation may not affect her ability to breastfeed.

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Interactions
Any drug known to have the potential to prolong the QT interval should not be used together with droperidol. Possible pharmacodynamic interactions can occur between droperidol and potentially arrhythmogenic agents such as class I or III antiarrhythmics, antihistamines that prolong the QT interval, antimalarials, calcium channel blockers, neuroleptics that prolong the QT interval, and antidepressants.
Caution should be used when patients are taking concomitant drugs known to induce hypokalemia or hypomagnesemia as they may precipitate QT prolongation and interact with droperidol. These would include diuretics, laxatives and supraphysiological use of steroid hormones with mineralocorticoid potential.
CNS depressant drugs (e.g. barbiturates, tranquilizers, opioids and general anesthetics) have additive or potentiating effects with droperidol. When patients have received such drugs, the dose of droperidol required will be less than usual. Following the administration of droperidol, the dose of other CNS depressant drugs should be reduced.
To report a case of QT prolongation associated with concomitant cyclobenzaprine and fluoxetine administration followed by torsade de pointes potentiated by droperidol. A 59-year-old white woman who had been receiving long-term fluoxetine and cyclobenzaprine therapy was admitted for Achilles tendon repair. Baseline QTc was prolonged at 497 msec. Prior to surgery, the patient received droperidol, an agent known to prolong the QT interval. During surgery the patient developed torsade de pointes, which progressed into ventricular fibrillation. On postoperative day 1, after cyclobenzaprine discontinuation, the QTc decreased toward normal (440 msec). Cyclobenzaprine shares anticholinergic effects, tachycardia, and dysrhythmic potential with the tricyclic antidepressants (TCAs). Fluoxetine is a known inhibitor of the CYP2D6 isoenzyme (along with CYP3A4 and CYP2C) and has been shown to increase TCA serum concentrations. The combination of cyclobenzaprine and fluoxetine resulted in significant QT prolongation in our patient that progressed to torsade de pointes after preoperative droperidol administration. Resolution of QT abnormalities after cyclobenzaprine discontinuation provided further evidence of a drug-induced etiology. Other possible medical and drug-related causes of torsade de pointes are reviewed and ruled out. ...
For more Interactions (Complete) data for DROPERIDOL (12 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Dog iv 25 mg/kg
LD50 Rabbit iv 11-13 mg/kg
LD50 Mouse im 195 mg/kg
LD50 Rat im 104-110 mg/kg.
For more Non-Human Toxicity Values (Complete) data for DROPERIDOL (11 total), please visit the HSDB record page.

[1]. Ann Emerg Med . 2003 Apr;41(4):546-58.

[2]. J Pharmacol Exp Ther . 1993 Aug;266(2):884-93.

[3]. Physiol Behav . 1991 Oct;50(4):825-30.

Therapeutic Uses
Adjuvants, Anesthesia; Antiemetics; Antipsychotic Agents; Dopamine Antagonists
Droperidol Injection is indicated to reduce the incidence of nausea and vomiting associated with surgical and diagnostic procedures. /Included in US product label/
Droperidol has been used preoperatively and as an adjunct during induction and maintenance of general anesthesia and as an adjunct to regional anesthesia. /NOT included in US product labeling/
Droperidol has been used in combination with an opiate analgesic, such as fentanyl, for neuroleptanalgesia as an anxiolytic and to potentially increase the analgesic effect of the opiate. However, because of the risk of serious adverse effects, the manufacturer no longer recommends these uses. /NOT included in US product labeling/
For more Therapeutic Uses (Complete) data for DROPERIDOL (11 total), please visit the HSDB record page.

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Drug Warnings
/BOXED WARNING/ WARNING: Cases of QT prolongation and/or torsade de pointes have been reported in patients receiving droperidol at doses at or below recommended doses. Some cases have occurred in patients with no known risk factors for QT prolongation and some cases have been fatal. Due to its potential for serious proarrhythmic effects and death, droperidol should be reserved for use in the treatment of patients who fail to show an acceptable response to other adequate treatments, either because of insufficient effectiveness or the inability to achieve an effective dose due to intolerable adverse effects from those drugs. Cases of QT prolongation and serious arrhythmias (e.g., torsade de pointes) have been reported in patients treated with droperidol. Based on these reports, all patients should undergo a 12-lead ECG prior to administration of droperidol to determine if a prolonged QT interval (i.e., QTc greater than 440 msec for males or 450 msec for females) is present. If there is a prolonged QT interval, droperidol should NOT be administered. For patients in whom the potential benefit of droperidol treatment is felt to outweigh the risks of potentially serious arrhythmias, ECG monitoring should be performed prior to treatment and continued for 2-3 hours after completing treatment to monitor for arrhythmias. Droperidol is contraindicated in patients with known or suspected QT prolongation, including patients with congenital long QT syndrome. Droperidol should be administered with extreme caution to patients who may be at risk for development of prolonged QT syndrome (e.g., congestive heart failure, bradycardia, use of a diuretic, cardiac hypertrophy, hypokalemia, hypomagnesemia, or administration of other drugs known to increase the QT interval). Other risk factors may include age over 65 years, alcohol abuse, and use of agents such as benzodiazepines, volatile anesthetics, and IV opiates. Droperidol should be initiated at a low dose and adjusted upward, with caution, as needed to achieve the desired effect.
Droperidol should be administered with extreme caution to patients who may be at risk for development of prolonged QT syndrome (e.g., congestive heart failure, bradycardia, use of a diuretic, cardiac hypertrophy, hypokalemia, hypomagnesemia, or administration of other drugs known to increase the QT interval). Other risk factors may include age over 65 years, alcohol abuse, and use of agents such as benzodiazepines, volatile anesthetics, and IV opiates. Droperidol should be initiated at a low dose and adjusted upward, with caution, as needed to achieve the desired effect.
Droperidol is contraindicated in patients with known or suspected QT prolongation (i.e., QTc interval greater than 440 msec for males or 450 msec for females). This would include patients with congenital long QT syndrome.
Droperidol is contraindicated in patients with known hypersensitivity to the drug.
For more Drug Warnings (Complete) data for DROPERIDOL (26 total), please visit the HSDB record page.

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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.

C22H22FN3O2

379.43

379.169

C, 69.64; H, 5.84; F, 5.01; N, 11.07; O, 8.43

548-73-2

3168

White to light tan, amorphous or microcrystalline powder

1.3±0.1 g/cm3

616.4±65.0 °C at 760 mmHg

148-149ºC

326.6±34.3 °C

0.0±1.8 mmHg at 25°C

1.636

4.22

1

4

6

28

615

0

FC1C([H])=C([H])C(=C([H])C=1[H])C(C([H])([H])C([H])([H])C([H])([H])N1C([H])([H])C([H])=C(C([H])([H])C1([H])[H])N1C(N([H])C2=C([H])C([H])=C([H])C([H])=C12)=O)=O

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)

3-[1-[4-(4-fluorophenyl)-4-oxobutyl]-3,6-dihydro-2H-pyridin-4-yl]-1H-benzimidazol-2-one

Inapsine; Dridol; Dehydrobenzperidol; Properidol; Droperidol; Droleptan; Inapsine; Janssen Brand of Droperidol; Kern Brand of Droperidol; Taylor Brand of Droperidol;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ~76 mg/mL (~200.3 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.59 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (6.59 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)