DT-Web

DB00450 - Droperidol


Identification
Name Droperidol
Accession Number DB00450 (APRD00939)
Type small molecule
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
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 379.4274
Groups approved
Monoisotopic Weight 379.169605168
Pharmacology
Indication Droperidol is ssed to produce tranquilization and to reduce the incidence of nausea and vomiting in surgical and diagnostic procedures.
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.
Absorption Completely absorbed following intramuscular administration.
Protein binding Not Available
Biotransformation Extensively metabolized.
Route of elimination 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
Interactions
Drug Interactions
Drug Mechanism of interaction
Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Brimonidine Droperidol may enhance the CNS depressant effect of brimonidine. Consider therapy modification.
Buprenorphine Droperidol may enhance the CNS depressant effect of CNS Depressants like buprenorphine. Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use.
Butabarbital Droperidol may enhance the CNS depressant effect of CNS Depressants like butabarbital. Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use.
Butalbital Droperidol may enhance the CNS depressant effect of CNS depressants such as butalbital. Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use.
Butorphanol Droperidol may enhance the CNS depressant effect of butorphanol. Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use.
Carisoprodol Droperidol may enhance the CNS depressant effect of carisoprodol. Consider dose reductions of droperidol or of other CNS agents with concomitant use.
Dihydrocodeine Enhanced CNS depressant effects are possible. Consider dose reduction of a CNS agent, if concurrent use is not avoidable.
Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Quinupristin This combination presents an increased risk of toxicity
Tacrine The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Droperidol, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Tetrabenazine May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects. May cause dopamine deficiency. Similar pharmacologic properties thus combination therapy will worsen the severity of sedative, parkinsonian, and extrapyramidal adverse effects.
Thiothixene May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Toremifene Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Trimethobenzamide Trimethobenzamide and Droperidol, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Trimipramine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Triprolidine Triprolidine and Droperidol, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
Trospium Trospium and Droperidol, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Voriconazole Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
Zuclopenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Food Interactions Not Available

Targets


D(2) dopamine receptor
Name D(2) dopamine receptor
Gene Name DRD2
Pharmacological action yes
Actions antagonist
References
  • 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
  • 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
  • Larson MD: The effect of antiemetics on pupillary reflex dilation during epidural/general anesthesia. Anesth Analg. 2003 Dec;97(6):1652-6. - Pubmed
  • 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. 2010 May;117(5):585-91. Epub 2010 Apr 1. - Pubmed
DTHybrid score 0.2523
Alpha-1A adrenergic receptor
Name Alpha-1A adrenergic receptor
Gene Name ADRA1A
Pharmacological action yes
Actions antagonist
References
  • 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
DTHybrid score 0.3013

Predictions


Id Partner name Gene Name Score
502 5-hydroxytryptamine 2A receptor HTR2A 0.1097
23 D(1A) dopamine receptor DRD1 0.1081
318 Alpha-2A adrenergic receptor ADRA2A 0.1021
632 Alpha-1B adrenergic receptor ADRA1B 0.0995
4119 Cytochrome P450 2D6 CYP2D6 0.0847
320 5-hydroxytryptamine 1A receptor HTR1A 0.0571
789 Alpha-1D adrenergic receptor ADRA1D 0.0568
638 D(3) dopamine receptor DRD3 0.0551
4512 Cytochrome P450 3A4 CYP3A4 0.0546
432 D(4) dopamine receptor DRD4 0.047
1588 Multidrug resistance protein 1 ABCB1 0.0447
590 5-hydroxytryptamine 2C receptor HTR2C 0.0439
629 Alpha-2B adrenergic receptor ADRA2B 0.0416
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0402
4200 Cytochrome P450 1A2 CYP1A2 0.0396
492 Histamine H1 receptor HRH1 0.0393
378 Alpha-2C adrenergic receptor ADRA2C 0.0388
103 Muscarinic acetylcholine receptor M1 CHRM1 0.0388
163 D(1B) dopamine receptor DRD5 0.0365
131 Synaptic vesicular amine transporter SLC18A2 0.0303
716 5-hydroxytryptamine 7 receptor HTR7 0.0257
725 5-hydroxytryptamine 1D receptor HTR1D 0.0251
6145 Solute carrier family 22 member 1 SLC22A1 0.0227
766 Beta-2 adrenergic receptor ADRB2 0.0225
274 Muscarinic acetylcholine receptor M5 CHRM5 0.0225
885 5-hydroxytryptamine 1B receptor HTR1B 0.022
450 Muscarinic acetylcholine receptor M4 CHRM4 0.0219
617 Muscarinic acetylcholine receptor M2 CHRM2 0.0215
436 5-hydroxytryptamine 2B receptor HTR2B 0.0209
193 Beta-1 adrenergic receptor ADRB1 0.0207
824 Sodium-dependent serotonin transporter SLC6A4 0.0203
51 Muscarinic acetylcholine receptor M3 CHRM3 0.0195
6016 Cytochrome P450 2C19 CYP2C19 0.0186
1256 5-hydroxytryptamine 6 receptor HTR6 0.017
713 Sodium-dependent dopamine transporter SLC6A3 0.0168
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.0166
3923 Cholinesterase BCHE 0.0165
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0163
465 Calmodulin CALM1 0.016
4757 Cytochrome P450 2C9 CYP2C9 0.016
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0155
4118 Cytochrome P450 3A5 CYP3A5 0.0153
6013 Cytochrome P450 2E1 CYP2E1 0.0149
587 Serum albumin ALB 0.0143
3876 Aromatic-L-amino-acid decarboxylase DDC 0.0139
6107 Cytochrome P450 3A7 CYP3A7 0.0136
3941 Amine oxidase [flavin-containing] A MAOA 0.0133
6030 Cytochrome P450 2B6 CYP2B6 0.0133
734 D1 dopamine receptor-interacting protein calcyon CALY 0.0096
6144 Solute carrier family 22 member 2 SLC22A2 0.0096
750 Voltage-dependent calcium channel gamma-1 subunit CACNG1 0.0087
5251 Carbonyl reductase [NADPH] 1 CBR1 0.0081
528 5-hydroxytryptamine 1E receptor HTR1E 0.0078
514 Potassium voltage-gated channel subfamily H member 6 KCNH6 0.0078
772 Potassium voltage-gated channel subfamily H member 7 KCNH7 0.0078
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0077
4924 Cytochrome P450 2C8 CYP2C8 0.0077
6859 Protein S100-A4 S100A4 0.0076
923 Glutamate receptor 3 GRIA3 0.0074
6147 Solute carrier family 22 member 3 SLC22A3 0.0062
341 5-hydroxytryptamine 3 receptor HTR3A 0.0062
124 Histamine H2 receptor HRH2 0.0055
3939 Amine oxidase [flavin-containing] B MAOB 0.0055
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.0054
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.0053
1561 Troponin C, slow skeletal and cardiac muscles TNNC1 0.0051
474 Acetylcholinesterase ACHE 0.0049
3947 Xanthine dehydrogenase/oxidase XDH 0.0048
174 Sigma 1-type opioid receptor SIGMAR1 0.0048
828 Phenylalanine-4-hydroxylase PAH 0.0046
3109 Phenylalanine-4-hydroxylase phhA 0.0046
921 Glutamate receptor 2 GRIA2 0.0045
6024 Cytochrome P450 1A1 CYP1A1 0.0045
6138 Multidrug resistance protein 3 ABCB4 0.0043
94 5-hydroxytryptamine 4 receptor HTR4 0.004
1636 Trace amine-associated receptor 1 TAAR1 0.0039
694 Matrix protein 2 M 0.0039
3426 Glutamine synthetase glnA 0.0037
3987 Glutamine synthetase GLUL 0.0037
6164 POU domain, class 5, transcription factor 1 POU5F1 0.0037
6023 Cytochrome P450 11B2, mitochondrial CYP11B2 0.0036
380 Cytochrome P450 17A1 CYP17A1 0.0035
427 Substance-P receptor TACR1 0.0034
118 Organic cation/carnitine transporter 2 SLC22A5 0.0034
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0034
4115 Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D 0.0032
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.0031
805 Cytochrome P450 11B1, mitochondrial CYP11B1 0.0031
1517 Beta-3 adrenergic receptor ADRB3 0.0031
20 Prostaglandin G/H synthase 1 PTGS1 0.0031
6106 Cytochrome P450 2C18 CYP2C18 0.003
4120 NADPH--cytochrome P450 reductase POR 0.003
6151 Monocarboxylate transporter 10 SLC16A10 0.0029
4113 Voltage-dependent L-type calcium channel subunit alpha-1F CACNA1F 0.0029
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0025
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0024
866 Large neutral amino acids transporter small subunit 2 SLC7A8 0.0024
4111 Voltage-dependent L-type calcium channel subunit alpha-1S CACNA1S 0.0024
5718 Cytochrome P450 2A6 CYP2A6 0.0023
245 Large neutral amino acids transporter small subunit 1 SLC7A5 0.0023
776 Bile salt export pump ABCB11 0.0021
1374 Natriuretic peptides B NPPB 0.0019
1827 Gap junction alpha-1 protein GJA1 0.0019
1908 Vascular cell adhesion protein 1 VCAM1 0.0019
6432 Transporter snf 0.0018
15 Voltage-dependent T-type calcium channel subunit alpha-1I CACNA1I 0.0018
6098 Potassium voltage-gated channel subfamily D member 2 KCND2 0.0017
6099 Potassium voltage-gated channel subfamily D member 3 KCND3 0.0017
4110 Voltage-dependent L-type calcium channel subunit beta-2 CACNB2 0.0017
1656 CYP2B protein CYP2B 0.0017
535 Voltage-dependent T-type calcium channel subunit alpha-1G CACNA1G 0.0017
464 Glutamate [NMDA] receptor subunit epsilon-2 GRIN2B 0.0016
964 Voltage-dependent T-type calcium channel subunit alpha-1H CACNA1H 0.0016
194 NADH dehydrogenase [ubiquinone] 1 subunit C2 NDUFC2 0.0016
164 Histamine H4 receptor HRH4 0.0016
153 Dopamine beta-hydroxylase DBH 0.0014
183 Vascular endothelial growth factor A VEGFA 0.0014
233 Potassium channel subfamily K member 2 KCNK2 0.0014
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0012
1360 Sphingomyelin phosphodiesterase SMPD1 0.0012
833 Organic cation/carnitine transporter 1 SLC22A4 0.0012
4114 Voltage-dependent L-type calcium channel subunit beta-3 CACNB3 0.0012
4112 Voltage-dependent L-type calcium channel subunit beta-4 CACNB4 0.0012
3810 Catechol O-methyltransferase COMT 0.0012
6047 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A PDE1A 0.0011
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0011
6100 BDNF/NT-3 growth factors receptor NTRK2 0.0011
333 Voltage-dependent L-type calcium channel subunit beta-1 CACNB1 0.0011
5692 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B PDE1B 0.0011
158 Sodium channel protein type 1 subunit alpha SCN1A 0.001
1898 Cytochrome P450 1B1 CYP1B1 0.0009
762 Voltage-dependent calcium channel subunit alpha-2/delta-1 CACNA2D1 0.0008
1618 High affinity nerve growth factor receptor NTRK1 0.0008
1086 Potassium voltage-gated channel subfamily KQT member 2 KCNQ2 0.0008
858 Potassium voltage-gated channel subfamily A member 1 KCNA1 0.0006
467 Delta-type opioid receptor OPRD1 0.0005
696 Kappa-type opioid receptor OPRK1 0.0005
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