Pipotiazine
Pipotiazine has actions similar to those of other phenothiazines. Among the different phenothiazine derivatives, it appears to be less sedating and to have a weak propensity for causing hypotension or potentiating the effects of CNS depressants and anesthetics. However, it produces a high incidence of extra pyramidal reactions. It is used for the maintenance treatment of chronic non-agitated schizophrenic patients. Symptoms of overdose include severe extrapyramidal manifestations, hypotension, lethargy and sedation.
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Structure for HMDB15558 (Pipotiazine)
C24H33N3O3S2
475.667
475.196333317
10-{3-[4-(2-hydroxyethyl)piperidin-1-yl]propyl}-N,N-dimethyl-10H-phenothiazine-2-slifonamide
pipotiazine
39860-99-6
CN(C)S(=O)(=O)C1=CC2=C(SC3=CC=CC=C3N2CCCN2CCC(CCO)CC2)C=C1
InChI=1S/C24H33N3O3S2/c1-25(2)32(29,30)20-8-9-24-22(18-20)27(21-6-3-4-7-23(21)31-24)14-5-13-26-15-10-19(11-16-26)12-17-28/h3-4,6-9,18-19,28H,5,10-17H2,1-2H3
JOMHSQGEWSNUKU-UHFFFAOYSA-N
This compound belongs to the class of chemical entities known as phenothiazines. These are polycyclic aromatic compounds containing a phenothiazine moiety, which is a linear tricyclic system that consists of a two benzene rings joined by a para-thiazine ring.
Chemical entities
Organic compounds
Organoheterocyclic compounds
Benzothiazines
Phenothiazines
Aromatic heteropolycyclic compounds
Not Available
Expected but not Quantified
Solid
Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available
Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available
Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available
Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available
Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available
Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available
Not Available
Not Available
Not Available
None
None
DB01621
Not Available
Not Available
Not Available
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Not Available
56598
Not Available
Not Available
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Not Available
HMDB15558
HMDB15558
Not Available
62867
Not Available
521177
Product: Ruxolitinib (S enantiomer)
Enzymes
- General function:
- Involved in monooxygenase activity
- Specific function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
- Gene Name:
- CYP3A4
- Uniprot ID:
- P08684
- Molecular weight:
- 57255.585
References
- Wojcikowski J, Boksa J, Daniel WA: Main contribution of the cytochrome P450 isoenzyme 1A2 (CYP1A2) to N-demethylation and 5-sulfoxidation of the phenothiazine neuroleptic chlorpromazine in human liver–A comparison with other phenothiazines. Biochem Pharmacol. 2010 Oct 15;80(8):1252-9. doi: 10.1016/j.bcp.2010.06.045. Epub 2010 Jul 6. [PubMed:20615392 ]
- General function:
- Involved in monooxygenase activity
- Specific function:
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
- Gene Name:
- CYP2C19
- Uniprot ID:
- P33261
- Molecular weight:
- 55944.565
References
- Wojcikowski J, Boksa J, Daniel WA: Main contribution of the cytochrome P450 isoenzyme 1A2 (CYP1A2) to N-demethylation and 5-sulfoxidation of the phenothiazine neuroleptic chlorpromazine in human liver–A comparison with other phenothiazines. Biochem Pharmacol. 2010 Oct 15;80(8):1252-9. doi: 10.1016/j.bcp.2010.06.045. Epub 2010 Jul 6. [PubMed:20615392 ]
- General function:
- Involved in monooxygenase activity
- Specific function:
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
- Gene Name:
- CYP2D6
- Uniprot ID:
- P10635
- Molecular weight:
- 55768.94
References
- Zhou SF: Polymorphism of human cytochrome P450 2D6 and its clinical significance: part II. Clin Pharmacokinet. 2009;48(12):761-804. doi: 10.2165/11318070-000000000-00000. [PubMed:19902987 ]
- Bhoopathy S, Xin B, Unger SE, Karnes HT: A novel incubation direct injection LC/MS/MS technique for in vitro drug metabolism screening studies involving the CYP 2D6 and the CYP 3A4 isozymes. J Pharm Biomed Anal. 2005 Apr 1;37(4):739-49. Epub 2004 Dec 30. [PubMed:15797796 ]
- General function:
- Involved in monooxygenase activity
- Specific function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
- Gene Name:
- CYP1A2
- Uniprot ID:
- P05177
- Molecular weight:
- 58406.915
References
- Wojcikowski J, Boksa J, Daniel WA: Main contribution of the cytochrome P450 isoenzyme 1A2 (CYP1A2) to N-demethylation and 5-sulfoxidation of the phenothiazine neuroleptic chlorpromazine in human liver–A comparison with other phenothiazines. Biochem Pharmacol. 2010 Oct 15;80(8):1252-9. doi: 10.1016/j.bcp.2010.06.045. Epub 2010 Jul 6. [PubMed:20615392 ]
- General function:
- Involved in G-protein coupled receptor protein signaling pathway
- Specific function:
- This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase
- Gene Name:
- DRD2
- Uniprot ID:
- P14416
- Molecular weight:
- 50618.9
References
- Oades RD, Rao ML, Bender S, Sartory G, Muller BW: Neuropsychological and conditioned blocking performance in patients with schizophrenia: assessment of the contribution of neuroleptic dose, serum levels and dopamine D2-receptor occupancy. Behav Pharmacol. 2000 Jun;11(3-4):317-30. [PubMed:11103886 ]
- Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. [PubMed:11873706 ]
- Wu S, Xing Q, Gao R, Li X, Gu N, Feng G, He L: Response to chlorpromazine treatment may be associated with polymorphisms of the DRD2 gene in Chinese schizophrenic patients. Neurosci Lett. 2005 Mar 7;376(1):1-4. Epub 2004 Dec 2. [PubMed:15694263 ]
- Wu SN, Gao R, Xing QH, Li HF, Shen YF, Gu NF, Feng GY, He L: Association of DRD2 polymorphisms and chlorpromazine-induced extrapyramidal syndrome in Chinese schizophrenic patients. Acta Pharmacol Sin. 2006 Aug;27(8):966-70. [PubMed:16867246 ]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
- Seeman P: Dopamine D2 receptors as treatment targets in schizophrenia. Clin Schizophr Relat Psychoses. 2010 Apr;4(1):56-73. doi: 10.3371/CSRP.4.1.5. [PubMed:20643630 ]
- Boireau A, Chambry J, Dubedat P, Farges G, Carruette AM, Zundel JL, Blanchard JC: Enhancing effect of dopamine blockers on evoked acetylcholine release in rat striatal slices: a classical D-2 antagonist response? Eur J Pharmacol. 1986 Aug 22;128(1-2):93-8. [PubMed:2875894 ]
- General function:
- Involved in G-protein coupled receptor protein signaling pathway
- Specific function:
- This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity
- Gene Name:
- HTR1A
- Uniprot ID:
- P08908
- Molecular weight:
- 46106.3
References
- Cosi C, Koek W: Agonist, antagonist, and inverse agonist properties of antipsychotics at human recombinant 5-HT(1A) receptors expressed in HeLa cells. Eur J Pharmacol. 2001 Dec 14;433(1):55-62. [PubMed:11755134 ]
- Newman-Tancredi A, Gavaudan S, Conte C, Chaput C, Touzard M, Verriele L, Audinot V, Millan MJ: Agonist and antagonist actions of antipsychotic agents at 5-HT1A receptors: a [35S]GTPgammaS binding study. Eur J Pharmacol. 1998 Aug 21;355(2-3):245-56. [PubMed:9760039 ]
- General function:
- Involved in G-protein coupled receptor protein signaling pathway
- Specific function:
- This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production
- Gene Name:
- HTR2A
- Uniprot ID:
- P28223
- Molecular weight:
- 52602.6
References
- Kusumi I, Takahashi Y, Suzuki K, Kameda K, Koyama T: Differential effects of subchronic treatments with atypical antipsychotic drugs on dopamine D2 and serotonin 5-HT2A receptors in the rat brain. J Neural Transm (Vienna). 2000;107(3):295-302. [PubMed:10821438 ]
- Yamada J, Sugimoto Y, Horisaka K: Serotonin2 (5-HT2) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) inhibits chlorpromazine- and haloperidol-induced hypothermia in mice. Biol Pharm Bull. 1995 Nov;18(11):1580-3. [PubMed:8593484 ]
- General function:
- Involved in G-protein coupled receptor protein signaling pathway
- Specific function:
- This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase
- Gene Name:
- DRD1
- Uniprot ID:
- P21728
- Molecular weight:
- 49292.8
References
- Kanba S, Suzuki E, Nomura S, Nakaki T, Yagi G, Asai M, Richelson E: Affinity of neuroleptics for D1 receptor of human brain striatum. J Psychiatry Neurosci. 1994 Jul;19(4):265-9. [PubMed:7918347 ]
Transporters
- General function:
- Involved in ion transmembrane transporter activity
- Specific function:
- Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)- N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin- dependent kinase II and LCK tyrosine kinase
- Gene Name:
- SLC22A1
- Uniprot ID:
- O15245
- Molecular weight:
- 61187.4
References
- Bednarczyk D, Ekins S, Wikel JH, Wright SH: Influence of molecular structure on substrate binding to the human organic cation transporter, hOCT1. Mol Pharmacol. 2003 Mar;63(3):489-98. [PubMed:12606755 ]