| Name | CYP3A4 |
|---|---|
| Synonyms | CP33; CYP3; HLP; CYP3A; CP34; CYP 3A4; CYP 3; CYP3A3… |
| Name | piperazine |
|---|---|
| CAS | piperazine |
| PubMed | Abstract | RScore(About this table) | |
|---|---|---|---|
| 12619053 | Greenblatt DJ, Von Moltke LL, Giancarlo GM, Garteiz DA: Human cytochromes mediating gepirone biotransformation at low substrate concentrations. Biopharm Drug Dispos. 2003 Mar;24(2):87-94. Biotransformation of gepirone to 1-(2-pyrimidinyl)-piperazine (1-PP) and 3'-OH-gepirone, as well as two other hydroxylated metabolites, was studied in vitro using a human liver microsomal preparation and heterologously expressed human CYP3A4 and CYP2D6. |
83(1,1,1,3) | Details |
| 12649383 | Cummins CL, Salphati L, Reid MJ, Benet LZ: In vivo modulation of intestinal CYP3A metabolism by P-glycoprotein: studies using the rat single-pass intestinal perfusion model. J Pharmacol Exp Ther. 2003 Apr;305(1):306-14. N-Methyl piperazine--homoPhe-vinylsulfone phenyl (K77), a peptidomimetic protease inhibitor (CYP3A/P-gp substrate), and midazolam (CYP3A substrate) were each perfused through a segment of rat ileum alone and with the P-gp inhibitor N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)-ethyl]-phenyl)- 9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamine (GG918). |
83(1,1,1,3) | Details |
| 19589229 | Antia U, Tingle MD, Russell BR: Metabolic interactions with piperazine-based 'party pill' drugs. J Pharm Pharmacol. 2009 Jul;61(7):877-82. CONCLUSIONS: Fluorophenylpiperazine, methoxyphenylpiperazine, chlorophenylpiperazine, methylbenzylpiperazine and methylenedioxybenzylpiperazine had significant inhibitory effects on CYP2D6, CYP1A2, CYP3A4, CYP2C19 and CYP2C9 isoenzymes but each piperazine had a different inhibitory profile. |
32(0,1,1,2) | Details |
| 11861813 | Cummins CL, Jacobsen W, Benet LZ: Unmasking the dynamic interplay between intestinal P-glycoprotein and CYP3A4. J Pharmacol Exp Ther. 2002 Mar;300(3):1036-45. The transport, metabolism, and intracellular levels of N-methyl piperazine--homoPhe-vinylsulfone phenyl (K77, a protease inhibitor; P-gp and CYP3A4 substrate) and felodipine (CYP3A4 substrate only) were measured across CYP3A4-transfected Caco-2 cells in the presence of an inhibitor of CYP3A4 and P-gp, cyclosporine (CsA), or an inhibitor of P-gp and not CYP3A4, GG918 (N-[4-[2-(1,2,3,4-tetrahydro-6,7- dimethoxy-2-isoquinolinyl)-ethyl]-phenyl]-9,10-dihydro-5-methoxy-9-oxo-4-a cridine carboxamine). |
5(0,0,0,5) | Details |
| 15640381 | Zhu M, Zhao W, Jimenez H, Zhang D, Yeola S, Dai R, Vachharajani N, Mitroka J: Cytochrome P450 3A-mediated metabolism of in human liver microsomes. Drug Metab Dispos. 2005 Apr;33(4):500-7. Epub 2005 Jan 7. mainly underwent N-dealkylation to 1-pyrimidinylpiperazine (1-PP), N-oxidation on the piperazine ring to N-oxide (Bu N-oxide), and hydroxylation to 3'-hydroxybuspirone (3'-OH-Bu), 5-hydroxybuspirone (5-OH-Bu), and 6'-hydroxybuspirone (6'-OH-Bu) in HLMs. Recombinant CYP3A4, CYP3A5, and CYP2D6 exhibited oxidation activities among nine P450 isoforms tested. |
3(0,0,0,3) | Details |
| 11038163 | Jacobsen W, Christians U, Benet LZ: In vitro evaluation of the disposition of A novel protease inhibitor. Drug Metab Dispos. 2000 Nov;28(11):1343-51. K11777 (N-methyl-piperazine--homoPhe-vinylsulfone-phenyl) is a potent, irreversible protease inhibitor. All three K11777 metabolites were formed by isolated CYP3A and their formation by human liver microsomes was inhibited by the CYP3A inhibitor cyclosporine (50 microM, 54-62% inhibition) and antibodies against human CYP3A4/5 (100 microg of antibodies/100 microg microsomal protein, 55-68% inhibition). |
3(0,0,0,3) | Details |
| 18950380 | Nishikawa H, Inoue T, Masui T, Izumi T, Nakagawa S, Koyama T: Pharmacokinetic interaction between tandospirone and fluvoxamine in the rat contextual conditioned fear stress model and its functional consequence: Involvement of cytochrome P450 3A4. Psychiatry Clin Neurosci. 2008 Oct;62(5):591-6. After testing the conditioned fear, plasma concentrations of tandospirone and its major metabolite 1-(2-pyrimidyl) piperazine were determined. |
5(0,0,0,5) | Details |
| 15056479 | Wojcikowski J, Pichard-Garcia L, Maurel P, Daniel WA: The metabolism of the piperazine-type phenothiazine neuroleptic perazine by the human cytochrome P-450 isoenzymes. Eur Neuropsychopharmacol. 2004 May;14(3):199-208. In human liver microsomes, the formation of perazine metabolites correlated significantly with the level of CYP1A2 and ethoxyrezorufin O-deethylase activity, as well as with the level of CYP3A4 and cyclosporin A oxidase activity. |
4(0,0,0,4) | Details |
| 11502731 | Cherstniakova SA, Bi D, Fuller DR, Mojsiak JZ, Collins JM, Cantilena LR: Metabolism of vanoxerine, 1-[2-[bis (4-fluorophenyl) methoxy] ethyl]-4-(3-phenylpropyl) piperazine, by human cytochrome P450 enzymes. Drug Metab Dispos. 2001 Sep;29(9):1216-20. Ketoconazole, a selective inhibitor of CYP3A, reduced GBR12909 biotransformation in human liver microsomes and primary hepatocytes by 92 +/- 2 and 92.4 +/- 0.4%, respectively. |
2(0,0,0,2) | Details |
| 12851040 | Jin L, Chen IW, Chiba M, Lin JH: Interaction with indinavir to enhance systemic exposure of an investigational HIV protease inhibitor in rats, dogs and monkeys. Xenobiotica. 2003 Jun;33(6):643-54. In vitro studies with liver microsomes revealed that compound A metabolism was mediated exclusively by CYP3A enzymes in rats, dogs and monkeys. |
2(0,0,0,2) | Details |
| 17368019 | Feng Y, Cameron MD, Frackowiak B, Griffin E, Lin L, Ruiz C, Schroter T, LoGrasso P: Structure-activity relationships, and drug metabolism and pharmacokinetic properties for indazole piperazine and indazole piperidine inhibitors of ROCK-II. Bioorg Med Chem Lett. 2007 Apr 15;17(8):2355-60. Epub 2006 Dec 21. Many of these inhibitors, especially the 2-amino substituted analogs for both series, are modest/potent CYP3A4 inhibitors as well. |
2(0,0,0,2) | Details |
| 17691920 | Caccia S: N-dealkylation of arylpiperazine derivatives: disposition and metabolism of the 1-aryl-piperazines formed. Curr Drug Metab. 2007 Aug;8(6):612-22. Most of them undergo extensive pre-systemic and systemic metabolism including CYP3A4-dependent N-dealkylation to 1-aryl-piperazines. Once formed they distribute extensively in tissues, including brain which is the target site of most arylpiperazine derivatives, and are then primarily biotransformed by CYP2D6-dependent oxidation to hydroxylates which are excreted as conjugates; only 1-(2-benzisothiazolyl)-piperazine is more susceptible to oxidation than to aromatic hydroxylation. |
2(0,0,0,2) | Details |
| 11114039 | Ramos L, Brignol N, Bakhtiar R, Ray T, Mc Mahon LM, Tse FL: High-throughput approaches to the quantitative analysis of ketoconazole, a potent inhibitor of cytochrome P450 3A4, in human plasma. Rapid Commun Mass Spectrom. 2000;14(23):2282-93. Ketoconazole, an -piperazine compound, is an orally active antimycotic agent. |
2(0,0,0,2) | Details |
| 14570760 | Warrington JS, von Moltke LL, Harmatz JS, Shader RI, Greenblatt DJ: The effect of age on biotransformation in rat and mouse liver microsomes. Drug Metab Dispos. 2003 Nov;31(11):1306-9. The role of specific isoforms in the conversion of SIL to its primary circulating metabolite, UK-103,320 (piperazine N-desmethyl in the mouse was also investigated using immunoinhibitory antibodies. Although CYP2C11 largely mediated UK-103,320 formation in the rat, UK-103,320 formation was principally inhibited by a CYP3A antibody in the mouse. |
2(0,0,0,2) | Details |
| 14566442 | Laine K, Ahokoski O, Huupponen R, Hanninen J, Palovaara S, Ruuskanen J, Bjorklund H, Anttila M, Rouru J: Effect of the novel anxiolytic drug deramciclane on the pharmacokinetics and pharmacodynamics of the CYP3A4 probe drug Eur J Clin Pharmacol. 2003 Dec;59(10):761-6. Epub 2003 Oct 18. |
2(0,0,0,2) | Details |
| 17220239 | Vincent SH, Reed JR, Bergman AJ, Elmore CS, Zhu B, Xu S, Ebel D, Larson P, Zeng W, Chen L, Dilzer S, Lasseter K, Gottesdiener K, Wagner JA, Herman GA: Metabolism and excretion of the dipeptidyl peptidase 4 inhibitor [14C] sitagliptin in humans. Drug Metab Dispos. 2007 Apr;35(4):533-8. Epub 2007 Jan 12. CYP3A4 was the major cytochrome P450 isozyme responsible for the limited oxidative metabolism of sitagliptin, with some minor contribution from CYP2C8. These metabolites were the N- and N-carbamoyl conjugates of parent drug, a mixture of hydroxylated derivatives, an ether of a hydroxylated metabolite, and two metabolites formed by oxidative desaturation of the piperazine ring followed by cyclization. |
1(0,0,0,1) | Details |
| 11978164 | Caley CF, Cooper CK: Ziprasidone: the fifth atypical antipsychotic. Ann Pharmacother. 2002 May;36(5):839-51. Metabolism of ziprasidone by aldehyde oxidase produces its only metabolite with potential pharmacologic activity; CYP3A4 also contributes to the metabolism of ziprasidone. DATA SYNTHESIS: Ziprasidone is a benzisothiazolyl piperazine-type atypical antipsychotic that shares the (2A)/ (2) (5-HT (2A)/D (2)) profile of the available atypical antipsychotics. |
1(0,0,0,1) | Details |
| 18238857 | Wen B, Ma L, Rodrigues AD, Zhu M: Detection of novel reactive metabolites of trazodone: evidence for CYP2D6-mediated bioactivation of m-chlorophenylpiperazine. Drug Metab Dispos. 2008 May;36(5):841-50. Epub 2008 Jan 31. Following incubations with trazodone in the presence of 1-(3'-chlorophenyl) piperazine (m-CPP), a major circulating and pharmacologically active metabolite of several antidepressants including trazodone, nefazodone, and etoperidone, was trapped with to afford the corresponding imine-sulfydryl adducts M4 and M5. In contrast to CYP3A4-dependent bioactivation of trazodone itself, formation of M4 was mediated specifically by CYP2D6, as evidenced by cDNA-expressed CYP2D6-catalyzing formation of M4 from m-CPP, strong inhibition of formation of M4 by quinidine, a specific CYP2D6 inhibitor, in both incubations of trazodone and m-CPP with human liver microsomes, and concentration-dependent inhibition of M4 formation by quinidine. |
1(0,0,0,1) | Details |
| 18238859 | Minato K, Suzuki R, Asagarasu A, Matsui T, Sato M: Biotransformation of 3-amino-5,6,7,8-tetrahydro-2-{4-[4-(quinolin-2-yl) piperazin-1-yl] butyl}qui nazolin-4 (3H)-one (TZB-30878), a novel (5-HT) 1A agonist/5-HT3 antagonist, in human hepatic cytochrome P450 enzymes. Drug Metab Dispos. 2008 May;36(5):831-40. Epub 2008 Jan 31. In addition, in vitro experiments in human liver microsomes with cytochrome P450 (P450)-specific inhibitors revealed that CYP3A4 was the major enzyme responsible for the metabolism of TZB-30878. This compound has quinazoline, piperazine, and quinoline rings. |
1(0,0,0,1) | Details |
| 16143527 | Powell NA, Clay EH, Holsworth DD, Bryant JW, Ryan MJ, Jalaie M, Edmunds JJ: Benzyl ether structure-activity relationships in a series of ketopiperazine-based renin inhibitors. Bioorg Med Chem Lett. 2005 Nov 1;15(21):4713-6. A 3-pyridinyloxymethyl substituent was also found to be equipotent as higher molecular weight analogs, and exhibited decreased CYP3A4 inhibition levels and improved pharmacokinetic properties. |
1(0,0,0,1) | Details |
| 14698036 | Staack RF, Paul LD, Springer D, Kraemer T, Maurer HH: Cytochrome P450 dependent metabolism of the new designer drug 1-(3-trifluoromethylphenyl) piperazine (TFMPP). Biochem Pharmacol. 2004 Jan 15;67(2):235-44. Studies using human CYPs showed that CYP1A2, CYP2D6 and CYP3A4 catalyzed TFMPP hydroxylation, with CYP2D6 being the most important enzyme accounting for about 81% of the net intrinsic clearance, calculated using the relative activity factor approach. |
1(0,0,0,1) | Details |
| 19904008 | Wojcikowski J, Daniel WA: Perazine at therapeutic drug concentrations inhibits human cytochrome P450 isoenzyme 1A2 (CYP1A2) and metabolism--an in vitro study. Pharmacol Rep. 2009 Sep-Oct;61(5):851-8. The aim of the present study was to estimate the inhibitory effect of perazine, a phenothiazine neuroleptic with piperazine structure in a side chain, on human CYP1A2 activity measured as a rate of 3-N- and 1-N-demethylation. Moreover, the influence of perazine on other metabolic pathways such as 7-N-demethylation (CYP1A2, CYP2C8/9, CYP3A4) and 8-hydroxylation (CYP3A4, CYP1A2, CYP2C8/9) was also determined. |
1(0,0,0,1) | Details |
| 20148045 | Antia U: 'Party pill' drugs--BZP and TFMPP. N Z Med J. 2009 Dec 11;122(1307):55-68. Their metabolism involves the hepatic P450 enzymes CYP2D6, CYP1A2 and CYP3A4 resulting in inhibited metabolism of other drugs and medicines, as well as compromised metabolism in poor metabolisers for CYP2D6. |
1(0,0,0,1) | Details |