5-methyl-8-(4-methylpiperazin-1-yl)-4-thia-2,9-diazatricyclo[8.4.0.0^{3,7}]tetradeca-1(10),2,5,7,11,13-hexaene

• ChemBase ID: 218
• Molecular Formular: C17H20N4S
• Molecular Mass: 312.4325
• Monoisotopic Mass: 312.14086766
• SMILES: s1c2=Nc3c(NC(=c2cc1C)N1CCN(CC1)C)cccc3
• Canonical SMILES: CN1CCN(CC1)C1=c2cc(sc2=Nc2c(N1)cccc2)C
• InChI: InChI=1S/C17H20N4S/c1-12-11-13-16(21-9-7-20(2)8-10-21)18-14-5-3-4-6-15(14)19-17(13)22-12/h3-6,11,18H,7-10H2,1-2H3
• InChIKey: WXPNDRBBWZMPQG-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 5-methyl-8-(4-methylpiperazin-1-yl)-4-thia-2,9-diazatricyclo[8.4.0.0^{3,7}]tetradeca-1(10),2,5,7,11,13-hexaene
• IUPAC Traditional name: 5-methyl-8-(4-methylpiperazin-1-yl)-4-thia-2,9-diazatricyclo[8.4.0.0^{3,7}]tetradeca-1(10),2,5,7,11,13-hexaene
• Brand Name: Olansek; Symbyax; Zydis; Zyprexa; Zyprexa Intramuscular; Zyprexa Zydis
• Synonyms: olanzapine; Olanzapine

Database IDs

• CAS Number: 132539-06-1
• PubChem SID: 160963681
• PubChem CID: 4585

CALCULATED PROPERTIES

JChem

• Acid pKa: 16.884417
• H Acceptors: 4
• H Donor: 1
• LogD (pH = 5.5): -1.3712059
• LogD (pH = 7.4): 1.4101064
• Log P: 2.736357
• Molar Refractivity: 108.7527 cm^3
• Polarizability: 35.520382 Å^3
• Polar Surface Area: 30.87 Å^2
• Rotatable Bonds: 1
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.65
• LOG S: -2.79
• Solubility (Water): 5.06e-01 g/l

PROPERTIES

Physical Property

• Hydrophobicity(logP): 2

DETAILS

DrugBank - DB00334

• Drug Groups: approved; investigational
• Description: Olanzapine is an atypical antipsychotic, approved by the FDA in 1996. Olanzapine is manufactured and marketed by the pharmaceutical company Eli Lilly and Company, whose patent for olanzapine proper ends in 2011.
• Indication: For the acute and maintenance treatment of schizophrenia and related psychotic disorders, as well as acute treatment of manic or mixed episodes of bipolar 1 disorder. Intramuscular olanzapine is indicated for the rapid control of agitated patients.
• Pharmacology: Olanzapine, an atypical antipsychotic agent, is used to treat both negative and positive symptoms of schizophrenia, acute mania with bipolar disorder, agitation, and psychotic symptoms in dementia. Future uses may include the treatment of obsessive-compulsive disorder and severe behavioral disorders in autism. Structurally and pharmacologically similar to clozapine, olanzapine binds to alpha(1), dopamine, histamine H1, muscarinic, and serotonin type 2 (5-HT₂) receptors.
• Toxicity: Symptoms of an overdose include tachycardia, agitation, dysarthria, decreased consciousness and coma. Death has been reported after an acute overdose of 0.45g, but also survival after an acute overdose of 1500g.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic
• Absorption: Well absorbed, with approximately 40% of the dose metabolized before reaching the systemic circulation.
• Half Life: 21 to 54 hours
• Protein Binding: 93%
• Elimination: It is eliminated extensively by first pass metabolism, with approximately 40% of the dose metabolized before reaching the systemic circulation. Following a single oral dose of 14C labeled olanzapine, 7% of the dose of olanzapine was recovered in the urine as unchanged drug, indicating that olanzapine is highly metabolized.
• Distribution: * 1000 L
• Clearance: * 12 to 47 L/h
• References: de Haan L, van Amelsvoort T, Rosien K, Linszen D: Weight loss after switching from conventional olanzapine tablets to orally disintegrating olanzapine tablets. Psychopharmacology (Berl). 2004 Sep;175(3):389-90. [Pubmed] ; Pollack MH, Simon NM, Zalta AK, Worthington JJ, Hoge EA, Mick E, Kinrys G, Oppenheimer J: Olanzapine augmentation of fluoxetine for refractory generalized anxiety disorder: a placebo controlled study. Biol Psychiatry. 2006 Feb 1;59(3):211-5. Epub 2005 Sep 1. [Pubmed] ; Sepede G, De Berardis D, Gambi F, Campanella D, La Rovere R, D'Amico M, Cicconetti A, Penna L, Peca S, Carano A, Mancini E, Salerno RM, Ferro FM: Olanzapine augmentation in treatment-resistant panic disorder: a 12-week, fixed-dose, open-label trial. J Clin Psychopharmacol. 2006 Feb;26(1):45-9. [Pubmed] ; Jakovljevic M, Sagud M, Mihaljevic-Peles A: Olanzapine in the treatment-resistant, combat-related PTSD--a series of case reports. Acta Psychiatr Scand. 2003 May;107(5):394-6; discussion 396. [Pubmed] ; McGlashan TH, Zipursky RB, Perkins D, Addington J, Miller TJ, Woods SW, Hawkins KA, Hoffman R, Lindborg S, Tohen M, Breier A: The PRIME North America randomized double-blind clinical trial of olanzapine versus placebo in patients at risk of being prodromally symptomatic for psychosis. I. Study rationale and design. Schizophr Res. 2003 May 1;61(1):7-18. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

REFERENCES

• de Haan L, van Amelsvoort T, Rosien K, Linszen D: Weight loss after switching from conventional olanzapine tablets to orally disintegrating olanzapine tablets. Psychopharmacology (Berl). 2004 Sep;175(3):389-90. Pubmed
• Pollack MH, Simon NM, Zalta AK, Worthington JJ, Hoge EA, Mick E, Kinrys G, Oppenheimer J: Olanzapine augmentation of fluoxetine for refractory generalized anxiety disorder: a placebo controlled study. Biol Psychiatry. 2006 Feb 1;59(3):211-5. Epub 2005 Sep 1. Pubmed
• Sepede G, De Berardis D, Gambi F, Campanella D, La Rovere R, D'Amico M, Cicconetti A, Penna L, Peca S, Carano A, Mancini E, Salerno RM, Ferro FM: Olanzapine augmentation in treatment-resistant panic disorder: a 12-week, fixed-dose, open-label trial. J Clin Psychopharmacol. 2006 Feb;26(1):45-9. Pubmed
• Jakovljevic M, Sagud M, Mihaljevic-Peles A: Olanzapine in the treatment-resistant, combat-related PTSD--a series of case reports. Acta Psychiatr Scand. 2003 May;107(5):394-6; discussion 396. Pubmed
• McGlashan TH, Zipursky RB, Perkins D, Addington J, Miller TJ, Woods SW, Hawkins KA, Hoffman R, Lindborg S, Tohen M, Breier A: The PRIME North America randomized double-blind clinical trial of olanzapine versus placebo in patients at risk of being prodromally symptomatic for psychosis. I. Study rationale and design. Schizophr Res. 2003 May 1;61(1):7-18. Pubmed