Investigational Drug Details
| Drug ID: | D091 |
| Drug Name: | Olanzapine |
| Synonyms: | |
| Type: | small molecule |
| DrugBank ID: | DB00334 |
| DrugBank Description: | Olanzapine is a thienobenzodiazepine classified as an atypical or second-generation antipsychotic agent.[A176996] The second-generation antipsychotics were introduced in the 90s and quickly widespread due to the presumed higher efficacy, less extrapyramidal side effects and fewer drug-drug interactions.[A177011] Olanzapine presents a very close resemblance to [clozapine] and it only differs by two additional methyl groups and the absence of a chloride moiety.[T554] It was obtained by the research of Eli Lilly and approved to be marketed in the US in 1996.[T548] |
| PubChem ID: | 135398745 |
| CasNo: | 132539-06-1 |
| Repositioning for NAFLD: | Yes |
| SMILES: | CN1CCN(CC1)C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 |
| Structure: |
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| InChiKey: | KVWDHTXUZHCGIO-UHFFFAOYSA-N |
| Molecular Weight: | 312.432 |
| DrugBank Targets: | 5-hydroxytryptamine receptor 2A; Dopamine D2 receptor; Dopamine D1 receptor; Dopamine D5 receptor; Dopamine D3 receptor; Dopamine D4 receptor; 5-hydroxytryptamine receptor 2C; 5-hydroxytryptamine receptor 3A; 5-hydroxytryptamine receptor 6; Histamine H1 receptor; Alpha-1A adrenergic receptor; Alpha-1B adrenergic receptor; Muscarinic acetylcholine receptor M1; Muscarinic acetylcholine receptor M2; Muscarinic acetylcholine receptor M3; Muscarinic acetylcholine receptor M4; D(1) dopamine receptor; Beta adrenergic receptor; 5-hydroxytryptamine receptor 1; GABA-A receptor (benzodiazepine site) |
| DrugBank MoA: | The activity of olanzapine is achieved by the antagonism of multiple neuronal receptors including the dopamine receptor D1, D2, D3 and D4 in the brain, the serotonin receptors 5HT2A, 5HT2C, 5HT3 and 5HT6, the alpha-1 adrenergic receptor, the histamine receptor H1 and multiple muscarinic receptors.[A176993, A176999] As abovementioned, olanzapine presents a wide profile of targets, however, its antagonistic effect towards the dopamine D2 receptor in the mesolimbic pathway is key as it blocks dopamine from having a potential action at the post-synaptic receptor. The binding of olanzapine to the dopamine D2 receptors is easily dissociable and hence, it allows for a certain degree of dopamine neurotransmission.[A177014] On the other hand, olanzapine acts in the serotonin 5HT2A receptors in the frontal cortex in a similar manner than the reported on dopamine D2 receptors. This determined effect allows for a decrease in adverse effects.[A177014] |
| DrugBank Pharmacology: | The effect of olanzapine in the D2 receptor is reported to produce the positive effects of this drug such as a decrease in hallucinations, delusions, disorganized speech, disorganized thought, and disorganized behavior. On the other hand, its effect on the serotonin 5HT2A receptor prevents the onset of anhedonia, flat affect, alogia, avolition and poor attention.[A177014] Based on the specific mechanism of action, olanzapine presents a higher affinity for the dopamine D2 receptor when compared to the rest of the dopamine receptor isotypes. This characteristic significantly reduces the presence of side effects.[T554] Clinical trials for the original use of olanzapine demonstrated significant effectiveness in the treatment of schizophrenia and bipolar disorder in adults and acute manic or mixed episodes associated with bipolar disorder in adolescents.[A177008] The effect of olanzapine on dopamine and serotonin receptors has been suggested to reduce chemotherapy-induced nausea and vomiting as those receptors are suggested to be involved in this process. For this effect, several clinical trials have been conducted and it has been shown that olanzapine can produce a significant increase in total control of nausea and vomiting.[A176993] In a high-level study of the effect of olanzapine for this condition, a complete response on the delay phase was observed in 84% of the individual and control of emesis of over 80% despite the phase.[A176999] |
| DrugBank Indication: | Olanzapine was initially used orally and intramuscularly for the chronic treatment of schizophrenia in patients over 13 years old and other psychiatric disorders such as bipolar I disorder including mixed or manic episodes.[A177014] Olanzapine is also indicated, in combination with lithium or valproate for the short-term treatment of acute manic or mixed episodes associated with bipolar I disorder in adults.[FDA label] As well, olanzapine is indicated, in combination with fluoxetine for the treatment of episodes of depression associated with bipolar disorder type 1 and treatment-resistant depression in patients over 10 years old.[A177014] Olanzapine is also approved for the management of psychomotor agitation associated with schizophrenia and bipolar I mania.[FDA label] Schizophrenia is a complex biochemical brain disorder that affects the person's ability to differentiate reality. It is usually observed as the presence of delusions, hallucinations, social withdrawal and disturbed thinking.[L5936] Bipolar disorder is a mental health condition defined by periods of extreme mood disturbances. It is categorized in different types from which type 1 is known to involve episodes of severe mania and often depression while type 2 presents less severe forms of mania.[L5939] |
| Targets: | |
| Therapeutic Category: | |
| Clinical Trial Progress: | |
| Latest Progress: |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L5693 | NCT03641352 | PHASE3 | UNKNOWN | NO | 2018-05-02 | 2018-08-22 | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T49 | Apolipoprotein L1 | APOL1 | Target is a single protein chain | O14791 | APOL1_HUMAN | Details | |
| T03 | Angiotensin-converting enzyme | ACE | INHIBITOR | Target is a single protein chain | P12821 | ACE_HUMAN | Details |
| T47 | Sialin | SLC17A5 | Target is a single protein chain | Q9NRA2 | SLC17A5_HUMAN | Details |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
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| Article ID | PMID | Source | Title |
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