Details of the Drug

General Information of Drug (ID: DMVHJLX)

Drug Name
Perospirone
Synonyms Lullan; SM-9018
Indication
Disease Entry ICD 11 Status REF
Psychotic disorder 6A20-6A25 Approved [1], [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 426.6
Topological Polar Surface Area (xlogp) 3.9
Rotatable Bond Count (rotbonds) 6
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 6
ADMET Property
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 5.7 mcg/L [3]
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 0.8-1.5 h [3]
Clearance
The clearance of drug is 425.5 +/- 150.3 L/h [4]
Elimination
Perospirone is mainly excreted via renal elimination, and only 0.4% of of total dose is excreted as unchanged drug following oral administration of 8mg perospirone [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 1.9 hours [3]
Metabolism
The drug is metabolized via the liver [5]
Vd
The volume of distribution (Vd) of drug is 1733 L [5]
Chemical Identifiers
Formula
C23H30N4O2S
IUPAC Name
(3aR,7aS)-2-[4-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]butyl]-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione
Canonical SMILES
C1CC[C@H]2[C@@H](C1)C(=O)N(C2=O)CCCCN3CCN(CC3)C4=NSC5=CC=CC=C54
InChI
InChI=1S/C23H30N4O2S/c28-22-17-7-1-2-8-18(17)23(29)27(22)12-6-5-11-25-13-15-26(16-14-25)21-19-9-3-4-10-20(19)30-24-21/h3-4,9-10,17-18H,1-2,5-8,11-16H2/t17-,18+
InChIKey
FBVFZWUMDDXLLG-HDICACEKSA-N
Cross-matching ID
PubChem CID
115368
ChEBI ID
CHEBI:94777
CAS Number
150915-41-6
DrugBank ID
DB08922
TTD ID
D0F6GV
INTEDE ID
DR1263

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
5-HT 2 receptor (5HT2R) TTYSN63 NOUNIPROTAC Modulator [6], [2]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Substrate [7]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Substrate [7]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7556).
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3 Perospirone. CNS Drugs. 2001;15(4):329-37; discussion 338.
4 Zou JJ, Liu L, Di B, Ding L, Zhu YB, Fan HW, Xiao DW, Wang GJ: Estimation of Perospirone in Human Plasma by LCCMSCMS and Its Application to Pharmacokinetics Study Chromatographia. 2008 August 1;68(3-4):239C243.
5 Torreele E, Bourdin Trunz B, Tweats D, Kaiser M, Brun R, Mazue G, Bray MA, Pecoul B: Fexinidazole--a new oral nitroimidazole drug candidate entering clinical development for the treatment of sleeping sickness. PLoS Negl Trop Dis. 2010 Dec 21;4(12):e923. doi: 10.1371/journal.pntd.0000923.
6 Pharmacological effects of zotepine and other antipsychotics on the central 5-HT2 receptors. Pharmacopsychiatry. 1993 Mar;26(2):53-8.
7 Steady-state pharmacokinetics of a new antipsychotic agent perospirone and its active metabolite, and its relationship with prolactin response. Ther Drug Monit. 2004 Aug;26(4):361-5.
8 Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
9 Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
10 CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
11 Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
12 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
13 Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
14 Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
15 Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
16 Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
17 Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
18 Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
19 Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
20 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
21 Differential expression and function of CYP2C isoforms in human intestine and liver. Pharmacogenetics. 2003 Sep;13(9):565-75.
22 Analysis of human cytochrome P450 2C8 substrate specificity using a substrate pharmacophore and site-directed mutants. Biochemistry. 2004 Dec 14;43(49):15379-92.
23 Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8.
24 PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9.
25 Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.
26 5-HT reuptake and 5-HT2 receptors modulate capsaicin-evoked hypothermia in rats. Neurosci Lett. 2008 Jan 17;430(3):191-6.
27 Torticollis under Cyclobenzaprine. Pharmacology. 2009 Jul 8;84(2):91-92.
28 Nordexfenfluramine causes more severe pulmonary vasoconstriction than dexfenfluramine. Am J Physiol Lung Cell Mol Physiol. 2004 Mar;286(3):L531-8.
29 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
30 Inhibition by the combined Ca2+ and 5-HT2 receptor antagonist nexopamil (LU 49938) of intracoronary thrombus formation in a canine model of arterial stenosis and intimal damage. J Cardiovasc Pharmacol. 1993 Nov;22(5):687-94.
31 Clinical pipeline report, company report or official report of Fabre-Kramer Pharmaceuticals.
32 Clinical pipeline report, company report or official report of Fabre-Kramer Pharmaceuticals.
33 Clinical pipeline report, company report or official report of Anamar.
34 Novel serotonin receptor 2 (5-HT2R) agonists and antagonists: a patent review (2004-2014).Expert Opin Ther Pat. 2016;26(1):89-106.