DT-Web

DB00372 - Thiethylperazine


Identification
Name Thiethylperazine
Accession Number DB00372 (APRD00323)
Type small molecule
Description A dopamine antagonist that is particularly useful in treating the nausea and vomiting associated with anesthesia, mildly emetic cancer chemotherapy agents, radiation therapy, and toxins. This piperazine phenothiazine does not prevent vertigo or motion sickness. (From AMA Drug Evaluations Annual, 1994, p457)
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 399.616
Groups approved
Monoisotopic Weight 399.180289323
Pharmacology
Indication For the treatment or relief of nausea and vomiting.
Mechanism of action Thiethylperazine is an antagonist at types 1, 2, and 4 dopamine receptors, 5-HT receptor types 2A and 2C, muscarinic receptors 1 through 5, alpha(1)-receptors, and histamine H1-receptors. Thiethylperazine's antipsychotic effect is due to antagonism at dopamine and serotonin type 2 receptors, with greater activity at serotonin 5-HT2 receptors than at dopamine type-2 receptors. This may explain the lack of extrapyramidal effects. Thiethylperazine does not appear to block dopamine within the tubero-infundibular tract, explaining the lower incidence of hyperprolactinemia than with typical antipsychotic agents or risperidone. Antagonism at muscarinic receptors, H1-receptors, and alpha(1)-receptors also occurs with thiethylperazine.
Absorption Not Available
Protein binding 60%
Biotransformation Not Available
Route of elimination Thiethylperazine is eliminated in the urine.
Toxicity Manifestations of acute overdosage of TORECAN (thiethylperazine) can be expected to reflect the CNS effects of the drug and include extrapyramidal symptoms (E.P.S), confusion and convulsions with reduced or absent reflexes, respiratory depression and hypotension.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Bromocriptine The phenothiazine decreases the effect of bromocriptine
Cisapride Increased risk of cardiotoxicity and arrhythmias
Dexfenfluramine Decreased anorexic effect, may increase psychotic symptoms
Diethylpropion Decreased anorexic effect, may increase psychotic symptoms
Fenfluramine Decreased anorexic effect, may increase psychotic symptoms
Gatifloxacin Increased risk of cardiotoxicity and arrhythmias
Grepafloxacin Increased risk of cardiotoxicity and arrhythmias
Guanethidine Thiethylperazine may decrease the effect of guanethidine.
Levofloxacin Increased risk of cardiotoxicity and arrhythmias
Mazindol Decreased anorexic effect, may increase psychotic symptoms
Phentermine Decreased anorexic effect, may increase psychotic symptoms
Phenylpropanolamine Decreased anorexic effect, may increase psychotic symptoms
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Food Interactions Not Available

Targets


D(2) dopamine receptor
Name D(2) dopamine receptor
Gene Name DRD2
Pharmacological action unknown
Actions antagonist
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Briani C, Cagnin A, Chierichetti F, Tiberio M, Battistin L, Pizzolato G: Thiethylperazine-induced parkinsonism: in vivo demonstration of dopamine D2 receptors blockade. Eur J Neurol. 2004 Oct;11(10):709-10. - Pubmed
DTHybrid score 0.3817
D(1A) dopamine receptor
Name D(1A) dopamine receptor
Gene Name DRD1
Pharmacological action unknown
Actions antagonist
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
DTHybrid score 0.3199
D(4) dopamine receptor
Name D(4) dopamine receptor
Gene Name DRD4
Pharmacological action unknown
Actions antagonist
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
DTHybrid score 0.1811

Predictions


Id Partner name Gene Name Score
502 5-hydroxytryptamine 2A receptor HTR2A 0.179
638 D(3) dopamine receptor DRD3 0.1365
163 D(1B) dopamine receptor DRD5 0.1166
320 5-hydroxytryptamine 1A receptor HTR1A 0.1062
4119 Cytochrome P450 2D6 CYP2D6 0.1056
590 5-hydroxytryptamine 2C receptor HTR2C 0.1027
556 Alpha-1A adrenergic receptor ADRA1A 0.1021
318 Alpha-2A adrenergic receptor ADRA2A 0.0975
629 Alpha-2B adrenergic receptor ADRA2B 0.0901
378 Alpha-2C adrenergic receptor ADRA2C 0.0861
632 Alpha-1B adrenergic receptor ADRA1B 0.0782
4512 Cytochrome P450 3A4 CYP3A4 0.0703
725 5-hydroxytryptamine 1D receptor HTR1D 0.0682
436 5-hydroxytryptamine 2B receptor HTR2B 0.0628
4200 Cytochrome P450 1A2 CYP1A2 0.0622
885 5-hydroxytryptamine 1B receptor HTR1B 0.0602
103 Muscarinic acetylcholine receptor M1 CHRM1 0.0538
492 Histamine H1 receptor HRH1 0.0509
716 5-hydroxytryptamine 7 receptor HTR7 0.0484
1588 Multidrug resistance protein 1 ABCB1 0.0406
617 Muscarinic acetylcholine receptor M2 CHRM2 0.0359
274 Muscarinic acetylcholine receptor M5 CHRM5 0.0356
450 Muscarinic acetylcholine receptor M4 CHRM4 0.0346
789 Alpha-1D adrenergic receptor ADRA1D 0.033
1256 5-hydroxytryptamine 6 receptor HTR6 0.0328
6145 Solute carrier family 22 member 1 SLC22A1 0.0315
51 Muscarinic acetylcholine receptor M3 CHRM3 0.0309
6016 Cytochrome P450 2C19 CYP2C19 0.0255
4118 Cytochrome P450 3A5 CYP3A5 0.0234
3876 Aromatic-L-amino-acid decarboxylase DDC 0.0222
4757 Cytochrome P450 2C9 CYP2C9 0.0215
6107 Cytochrome P450 3A7 CYP3A7 0.0208
587 Serum albumin ALB 0.0206
6013 Cytochrome P450 2E1 CYP2E1 0.0197
528 5-hydroxytryptamine 1E receptor HTR1E 0.0195
734 D1 dopamine receptor-interacting protein calcyon CALY 0.0169
465 Calmodulin CALM1 0.0168
174 Sigma 1-type opioid receptor SIGMAR1 0.0158
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0155
341 5-hydroxytryptamine 3 receptor HTR3A 0.0153
3923 Cholinesterase BCHE 0.0135
3941 Amine oxidase [flavin-containing] A MAOA 0.0134
824 Sodium-dependent serotonin transporter SLC6A4 0.0117
866 Large neutral amino acids transporter small subunit 2 SLC7A8 0.0114
6144 Solute carrier family 22 member 2 SLC22A2 0.011
245 Large neutral amino acids transporter small subunit 1 SLC7A5 0.0107
5251 Carbonyl reductase [NADPH] 1 CBR1 0.0102
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0101
4924 Cytochrome P450 2C8 CYP2C8 0.0099
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0088
750 Voltage-dependent calcium channel gamma-1 subunit CACNG1 0.0087
6164 POU domain, class 5, transcription factor 1 POU5F1 0.0085
6030 Cytochrome P450 2B6 CYP2B6 0.0081
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.0078
193 Beta-1 adrenergic receptor ADRB1 0.0078
6151 Monocarboxylate transporter 10 SLC16A10 0.0076
713 Sodium-dependent dopamine transporter SLC6A3 0.0075
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0074
923 Glutamate receptor 3 GRIA3 0.0074
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.0074
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.0071
3939 Amine oxidase [flavin-containing] B MAOB 0.007
153 Dopamine beta-hydroxylase DBH 0.0068
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0063
131 Synaptic vesicular amine transporter SLC18A2 0.006
3426 Glutamine synthetase glnA 0.0056
3987 Glutamine synthetase GLUL 0.0056
124 Histamine H2 receptor HRH2 0.0055
3810 Catechol O-methyltransferase COMT 0.0054
6024 Cytochrome P450 1A1 CYP1A1 0.0051
6147 Solute carrier family 22 member 3 SLC22A3 0.0047
921 Glutamate receptor 2 GRIA2 0.0045
6106 Cytochrome P450 2C18 CYP2C18 0.0042
6859 Protein S100-A4 S100A4 0.0041
118 Organic cation/carnitine transporter 2 SLC22A5 0.0041
474 Acetylcholinesterase ACHE 0.0041
94 5-hydroxytryptamine 4 receptor HTR4 0.004
694 Matrix protein 2 M 0.0039
164 Histamine H4 receptor HRH4 0.0039
464 Glutamate [NMDA] receptor subunit epsilon-2 GRIN2B 0.0038
766 Beta-2 adrenergic receptor ADRB2 0.0036
6023 Cytochrome P450 11B2, mitochondrial CYP11B2 0.0036
380 Cytochrome P450 17A1 CYP17A1 0.0035
427 Substance-P receptor TACR1 0.0034
805 Cytochrome P450 11B1, mitochondrial CYP11B1 0.0031
5718 Cytochrome P450 2A6 CYP2A6 0.003
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0029
1561 Troponin C, slow skeletal and cardiac muscles TNNC1 0.0027
776 Bile salt export pump ABCB11 0.0027
1898 Cytochrome P450 1B1 CYP1B1 0.0022
3947 Xanthine dehydrogenase/oxidase XDH 0.002
4113 Voltage-dependent L-type calcium channel subunit alpha-1F CACNA1F 0.0018
15 Voltage-dependent T-type calcium channel subunit alpha-1I CACNA1I 0.0018
20 Prostaglandin G/H synthase 1 PTGS1 0.0017
535 Voltage-dependent T-type calcium channel subunit alpha-1G CACNA1G 0.0017
964 Voltage-dependent T-type calcium channel subunit alpha-1H CACNA1H 0.0016
4115 Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D 0.0015
4111 Voltage-dependent L-type calcium channel subunit alpha-1S CACNA1S 0.0015
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.0014
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