548-73-2 Usage
Description
DROPERIDOL is a butyrophenone with potent antidopaminergic (D2) activity and mild α2-blocking actions. It is a D1 and D2 dopamine receptor antagonist, an H2 antihistamine, and a D1DR and D2DR inhibitor. DROPERIDOL is used for its antipsychotic, sedative, and antishock properties, and it potentiates the action of drugs for narcosis. It is also an effective antiemetic and has been used for premedication and in neuroleptanaesthesia. DROPERIDOL is a pale yellow solid and is marketed under the brand name Inapsine.
Used in Anesthesiology:
DROPERIDOL is used as a preanesthetic neuroleptic or as an antiemetic. It is often used in combination with the narcotic agent fentanyl (Sublimaze) for neuroleptanalgesia, which helps maintain a calm state of the patient with indifference to surroundings but still able to cooperate with the surgeon.
Used in Psychiatry:
DROPERIDOL is used as an antipsychotic for the treatment of psychomotor excitement and hallucinations. It is particularly useful in managing symptoms such as agitation and delirium.
Used in Postoperative Care:
DROPERIDOL has been reintroduced and licensed at lower doses for the prevention of postoperative nausea and vomiting. It has an onset of 3-10 minutes after intravenous injection and a duration of action of 6-12 hours.
Used in Chemotherapy-Induced Nausea and Vomiting:
DROPERIDOL is used in the management of chemotherapy-induced nausea and vomiting, often in conjunction with an opioid analgesic such as fentanyl to maintain the patient in a calm state of neuroleptanalgesia.
Used in Combination Therapy:
DROPERIDOL is used in combination with certain forms of inhalation anesthetics, which may produce peripheral vasodilation and hypotension. It is also used in combination with centrally acting acetylcholinesterase inhibitors, which may increase the risk of antipsychotic-related extrapyramidal symptoms (EPS).
Used in Pharmaceutical Industry:
DROPERIDOL is used as an organofluorine compound in the pharmaceutical industry for its various applications, including the management of chemotherapy-induced nausea and vomiting, and in conjunction with an opioid analgesic for maintaining a calm state of neuroleptanalgesia.
Originator
Dehydrobenzperidol,Janssen,W. Germany,1963
Manufacturing Process
A mixture of 10 parts of γ-chloro-4-fluorobutyrophenone, 5.5 parts of 1-
(1,2,3,6-tetrahydro-4-pyridyl)-2-benzimidazolinone, 4 parts of sodium
carbonate, and 0.1 part of potassium iodide in 176 parts of 4-methyl-2-
pentanone is stirred and refluxed for 64 hours. The cooled reaction mixture is
filtered and the solvent is evaporated from the filtrate to leave an oily residue
which is dissolved in toluene. The toluene solution is filtered and the solvent is
evaporated. The resultant residue is recrystallized from a mixture of 32 parts
of ethyl acetate and 32 parts of diisopropyl ether to give 1-[1-[(4-fluorobenzoyl)propyl]-1,2,3,6-tetrahydro-4-pyridyl]-2-benzimidazolinone
hydrate melting at about 145°-146.5°C.
Therapeutic Function
Tranquilizer
Biochem/physiol Actions
D1, D2 dopamine receptor antagonist; butyrophenone antipsychotic and anti-emetic.
Clinical Use
#N/A
Synthesis
Droperidol, 1-[1-[3-(p-fluorobenzoyl)propyl]-1,2,3,6,4-piridyl]-2-benzymidazolinone (6.3.11), is synthesized from 1-benzyl-3-carbethoxypiperidin-4-one (3.1.47),
which is reacted with o-phenylendiamine. Evidently, the first derivative that is formed
under the reaction conditions, 1,5-benzdiazepine, rearranges into 1-(1-benzyl-1,2,3,6-
tetrahydro-4-piridyl)-2-benzymidazolone (6.3.9). Debenzylation of the resulting product
with hydrogen over a palladium catalyst into 1-(1,2,3,6-tetrahydro-4-piridyl)-2-benzimidazolon (6.3.10) and subsequent alkylation of this using 4′-chloro-4-fluorobutyrophenone
(6.3.4) yields droperidol (6.3.11) [47–49].
Drug interactions
Potentially hazardous interactions with other drugsAnaesthetics: enhanced hypotensive effect; effects of
thiopental enhanced.Analgesics: increased risk of ventricular arrhythmias
with methadone; increased risk of convulsions with
tramadol; enhanced hypotensive and sedative effects
with opioids.Anti-arrhythmics increased risk of ventricular
arrhythmias with anti-arrhythmics that prolong
the QT interval, e.g. procainamide, disopyramide,
dronedarone and amiodarone - avoid.Antibacterials: increased risk of ventricular
arrhythmias with moxifloxacin and macrolides -
avoid; increased risk of ventricular arrhythmias with
delamanid.Antidepressants: increased risk of ventricular
arrhythmias with fluoxetine, fluvoxamine, sertraline
or tricyclics - avoid; possible increased risk of
convulsions with vortioxetine.Antiepileptics: convulsive threshold lowered.Antimalarials: avoid with artemether/lumefantrine
and piperaquine with artenimol; increased risk
of ventricular arrhythmias with chloroquine,
hydroxychloroquine or quinine - avoid.Antipsychotics: increased risk of ventricular
arrhythmias with amisulpride, pimozide, sulpiride,
phenothiazines that prolong QT interval or
haloperidol - avoid; possibly increased risk of
ventricular arrhythmias with risperidone.Antivirals: concentration possibly increased with ritonavirAnxiolytics and hypnotics: increased sedative effects.Atomoxetine: increased risk of ventricular
arrhythmias.Beta-blockers: enhanced hypotensive effect;
increased risk of ventricular arrhythmias with sotalol
- avoid.Cytotoxics: increased risk of ventricular arrhythmias
with arsenic trioxide and possibly ceritinib.Desferrioxamine: avoid concomitant use.Diuretics: enhanced hypotensive effect.Hormone antagonists: increased risk of ventricular
arrhythmias with tamoxifen - avoid.Lithium: increased risk of extrapyramidal side effects
and possibly neurotoxicity.Pentamidine: increased risk of ventricular
arrhythmias - avoid.Tacrolimus: increased risk of ventricular arrhythmias
- avoid.
Metabolism
Extensively metabolised in the liver, and undergoes
oxidation, dealkylation, demethylation and hydroxylation
by cytochrome P450 isoenzymes 1A2 and 3A4, and to a
lesser extent by 2C19. The metabolites are inactive.
About 75% of a dose is excreted in the urine, with 1%
being excreted unchanged; 11% appears in the faeces.
Check Digit Verification of cas no
The CAS Registry Mumber 548-73-2 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 5,4 and 8 respectively; the second part has 2 digits, 7 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 548-73:
(5*5)+(4*4)+(3*8)+(2*7)+(1*3)=82
82 % 10 = 2
So 548-73-2 is a valid CAS Registry Number.
InChI:InChI=1/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)
548-73-2Relevant articles and documents
Rearrangement of spiro-benzimidazolines: preparation of N-alkenyl- and N-alkyl-benzimidazol-2-ones
Kuethe, Jeffrey T.,Varon, Jack,Childers, Karla G.
, p. 11489 - 11502 (2008/03/13)
A synthetically useful protocol has been developed for the preparation of highly functionalized N-alkenyl-benzimidazol-2-ones. Reaction of commercially available o-phenylenediamines with variously substituted cyclic ketones provides spiro-benzimidazolines. Treatment of these spiro-benzimidazolines with triphosgene in the presence of potassium carbonate results in rapid rearrangement and formation of N-alkenyl-benzimidazol-2-ones in modest to excellent yield for the two-step sequence. Extension of this methodology toward the preparation of a μ opiate receptor antagonist and droperidol, a potent antiemetic and antipsychotic agent, currently a marketed pharmaceutical is also described. Upon treatment of spiro-benzimidazolines with triphosgene in the presence of sodium triacetoxyborohydride, N-alkyl-benzimidazol-2-ones were formed.
Phenylbutanol derivatives
-
, (2008/06/13)
Butyrophenone derivatives having excellent psychotropic activity and represented by the formula, SPC1 Wherein A represents a single or double bond linkage; R1 represents a hydrogen atom or a C1 - C4 alkyl group; R2, which is present only in case A represents a single bond linkage, represents a hydrogen atom, or a hydroxyl, C1 - C4 alkyl, or C1 - C4 alkoxy group; R3 represents a hydrogen atom, or a piperidino, pyrrolidino, morpholino, furyl, thienyl, C1 - C4 alkylamino, benzylamino, unsubstituted or halogen-substituted phenyl group, etc.; and X represents a hydrogen or halogen atom, or a C1 - C4 alkyl, C1 - C4 alkoxy, or trifluoromethyl group, can be prepared by reducing a benzoylpropionamide derivative of the formula, SPC2 Wherein A, R1, R2, R3 and X have the same meanings as defined above, to a phenylbutanol derivative of the formula, SPC3