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 after intramuscular injection. The pharmacological effects of haloperidol begin to appear within 3–10 minutes after intramuscular or intravenous injection, but peak pharmacological action may not occur until 30 minutes later. Sedative and tranquilizing effects of haloperidol typically last 2–4 hours after a single intramuscular or intravenous injection; altered consciousness may persist for up to 12 hours. Haloperidol has been reported to cross the blood-brain barrier and distribute into the cerebrospinal fluid. Haloperidol has been reported to cross the placenta, but data are limited. It is unclear whether haloperidol is distributed into breast milk. For more complete data on the absorption, distribution, and excretion of haloperidols (7 in total), please visit the HSDB records page. Metabolism/Metabolites Extensively metabolized. Although the exact metabolic pathway of haloperidol is not fully established, the drug is metabolized in the liver. The butyrophenone moiety of haloperidol is metabolized to p-fluorophenylacetic acid, which then conjugates with glycine. The nitrogenous moiety of domperidone appears to be metabolized to benzimidazolone and p-hydroxypiperidine.

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Biological half-life
Bilingual distribution. The rapid distribution phase is 1.4 ± 0.5 min, and the slow distribution phase is 14.3 ± 6.5 min. The elimination half-life in adults is 134 ± 13 min, which may be prolonged in elderly patients. The elimination half-life in children is 101.5 ± 26.4 min.
…Domperidone is rapidly absorbed after intramuscular injection, and the plasma concentration profile of the parent drug conforms to a two-compartment model kinetics. The plasma half-life is approximately 130 minutes…

Effects During Pregnancy and Lactation
◉ Overview of Medications Used During Lactation
Due to a lack of information regarding long-term use of haloperidol during lactation, alternative medications may be preferred, especially when breastfeeding newborns or premature infants. Single or short-term use during lactation (e.g., during surgery) is unlikely to have adverse effects on breastfed infants, especially if the infant is older than 2 months. If the mother uses the medication multiple times, the infant's drowsiness should be monitored, especially in younger, exclusively breastfed infants and when used in combination with other psychotropic medications. ◉ Effects on Breastfed Infants
A randomized study compared infants who received patient-controlled analgesia (PCA) after cesarean section, whose mothers received either morphine or morphine plus haloperidol. On days 1 and 2 after birth, infants whose mothers received haloperidol had lower Neonatal Neurological and Adaptive Abilities Scores (NACS) than infants who received morphine alone.
A breastfed infant whose mother was taking haloperidol (the extent of breastfeeding was not specified) showed a slight decrease in intellectual development during testing, but the mother had also taken olanzapine, clonazepam, sertraline, thioridazine, and valproic acid during breastfeeding.
◉ Effects on Lactation and Breast Milk
Hyperprolactinemia has been reported in patients taking haloperidol long-term and those using it for short periods during surgery. Prolactin levels in established lactating mothers may not affect their ability to breastfeed.

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Drug Interactions
Any drug known to prolong the QT interval should not be used with haloperidol. Haloperidol may have pharmacodynamic interactions with potentially arrhythmic drugs, such as class I or III antiarrhythmics, QT-prolonging antihistamines, antimalarial drugs, calcium channel blockers, QT-prolonging antipsychotics, and antidepressants.
Caution should be exercised when patients are taking medications known to induce hypokalemia or hypomagnesemia, as these medications may induce QT interval prolongation and interact with haloperidol. These medications include diuretics, laxatives, and supraphysiological doses of mineralocorticoid-like steroid hormones.
Central nervous system depressants (such as barbiturates, sedatives, opioids, and general anesthetics) have additive or enhancing effects with haloperidol. When a patient has taken such medications, the required dose of haloperidol will be lower than the usual dose. After taking haloperidol, the dose of other central nervous system depressants should be reduced.
This article reports a case of QT interval prolongation due to concomitant use of cyclobenzaprine and fluoxetine, followed by torsades de pointes, which was exacerbated by haloperidol. A 59-year-old white woman, on long-term fluoxetine and cyclobenzaprine, was admitted for Achilles tendon repair surgery. The baseline QTc interval was prolonged to 497 milliseconds. Preoperatively, the patient was taking haloperidol, a drug known to prolong the QT interval. During the procedure, the patient developed torsades de pointes, which progressed to ventricular fibrillation. On postoperative day 1, after discontinuing cyclobenzaline, the QTc interval gradually returned to normal (440 ms). Cyclobenzaline has similar anticholinergic effects, tachycardia, and arrhythmia risk as tricyclic antidepressants (TCAs). Fluoxetine is a known inhibitor of the CYP2D6 isoenzyme (as well as CYP3A4 and CYP2C) and has been shown to increase serum concentrations of tricyclic antidepressants (TCAs). In this case, the patient's preoperative use of haloperidol, combined with cyclobenzaline and fluoxetine, led to a significant prolongation of the QT interval, which progressed to torsades de pointes. The normalization of the QT interval after discontinuation of cyclobenzaline further confirmed the drug-induced cause. This article also reviewed and ruled out other medical conditions and drug-related causes that could lead to torsades de pointes ventricular tachycardia. ...
For more complete data on interactions of dropiperidine (12 in total), please visit the HSDB record page.

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Non-human toxicity values
Canine intravenous LD50: 25 mg/kg
Rabbit intravenous LD50: 11-13 mg/kg
Mouse intramuscular LD50: 195 mg/kg
Rat intramuscular LD50: 104-110 mg/kg.
For more complete data on non-human toxicity values of dropiperidine (11 in 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

Adjunctive use, anesthesia; antiemetic; antipsychotic; dopamine antagonist. Haloperidol injection is indicated to reduce the incidence of nausea and vomiting during surgery and diagnostic procedures. /Included on US product label/
Haloperidol was previously used preoperatively and as adjunctive therapy during induction and maintenance of general anesthesia, as well as as adjunctive therapy for regional anesthesia. /Not included on US product label/
Haloperidol was previously used in combination with opioid analgesics (such as fentanyl) for neurogenic analgesia, as an anxiolytic, and may enhance the analgesic effect of opioids. However, due to the risk of serious adverse reactions, the manufacturer no longer recommends these uses. /Not included on US product label/
For more complete data on the therapeutic uses of haloperidol (11 in total), please visit the HSDB record page.

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Drug Warning
/Black Box Warning/ Warning: Cases of QT prolongation and/or torsades de pointes have been reported in patients taking haloperidol, even at doses equal to or lower than the recommended dose. Some cases occurred in patients without known risk factors for QT prolongation, and some even resulted in death. Due to the serious proarrhythmic effects and risk of death associated with haloperidol, it should only be used in patients who have failed other adequate treatments, possibly due to inadequate efficacy or intolerance to the effective dose caused by the adverse effects of these drugs. Cases of QT prolongation and serious arrhythmias (such as torsades de pointes) have been reported in patients taking haloperidol. Based on these reports, all patients should undergo a 12-lead electrocardiogram before taking haloperidol to determine the presence of QT prolongation (i.e., a QTc interval greater than 440 ms in men or greater than 450 ms in women). Haloperidol should not be taken if QT prolongation is present. For patients for whom the potential benefit of haloperidol treatment outweighs the potential risk of serious arrhythmias, electrocardiographic monitoring should be performed before treatment and continued for 2-3 hours after treatment to observe for any arrhythmias. Haloperidol is contraindicated in patients with known or suspected QT interval prolongation, including those with congenital long QT syndrome. Haloperidol should be used with extreme caution in patients at risk of QT interval prolongation (e.g., congestive heart failure, bradycardia, use of diuretics, cardiac hypertrophy, hypokalemia, hypomagnesemia, or use of other medications known to prolong the QT interval). Other risk factors may include age over 65 years, alcoholism, and use of benzodiazepines, volatile narcotics, and intravenous opioids. Haloperidol should be started at a low dose and cautiously increased gradually as needed to achieve the desired effect. Haloperidol should be used with extreme caution in patients at risk of QT prolongation syndrome (e.g., congestive heart failure, bradycardia, use of diuretics, cardiomegaly, hypokalemia, hypomagnesemia, or use of other medications known to prolong the QT interval). Other risk factors may include age over 65 years, alcoholism, and use of benzodiazepines, volatile narcotics, and intravenous opioids. Haloperidol should be started at a low dose and cautiously increased gradually as needed to achieve the desired effect. Haloperidol is contraindicated in patients with known or suspected QT prolongation (i.e., a QTc interval greater than 440 ms in men or greater than 450 ms in women). This includes patients with congenital long QT syndrome. Haloperidol is contraindicated in patients with known hypersensitivity to this drug. For more complete data on haloperidol (26 in total), please visit the HSDB record page. Pharmacodynamics Haloperidol has significant sedative and hypnotic effects. It can relieve anxiety, inducing a state of mental relaxation and apathy while maintaining reflexive alertness. Haloperidol has antiemetic effects, as evidenced by its antagonistic effect against apomorphine in dogs. It can reduce the incidence of nausea and vomiting during surgery and provide antiemetic protection postoperatively. Haloperidol can enhance the effects of other central nervous system depressants. It produces mild alpha-adrenergic blockade, peripheral vasodilation, and reduces the pressor effect of adrenaline. It can cause hypotension and decreased peripheral vascular resistance, and may reduce pulmonary artery pressure (especially in cases of abnormally high pulmonary artery pressure). It may reduce the incidence of adrenaline-induced arrhythmias, but does not prevent other types of 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.)