Repositioning Candidate Details
| Candidate ID: | R0065 |
| Source ID: | DB00246 |
| Source Type: | approved |
| Compound Type: | small molecule |
| Compound Name: | Ziprasidone |
| Synonyms: | |
| Molecular Formula: | C21H21ClN4OS |
| SMILES: | ClC1=C(CCN2CCN(CC2)C2=NSC3=CC=CC=C23)C=C2CC(=O)NC2=C1 |
| Structure: |
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| DrugBank Description: | Ziprasidone is classified as an atypical antipsychotic and is used primarily to treat schizophrenia and bipolar disorder.[A180748] It is effective at reducing the rate and time of relapses in schizophrenia, and can be used to treat manic episodes in bipolar disorder although the mechanism of action is unknown.[A180748] |
| CAS Number: | 146939-27-7 |
| Molecular Weight: | 412.936 |
| DrugBank Indication: | In it's oral form, ziprasidone is approved for the treatment of Schizophrenia, as monotherapy for acute treatment of manic or mixed episodes related to bipolar I disorder, and as adjunctive therapy to lithium or valproate for maintenance treatment of bipolar I disorder.[L7342] The injectable formulation is approved only for treatment of acute agitation in schizophrenia.[L7342] |
| DrugBank Pharmacology: | Ziprasidone is classified as a "second generation" or "atypical" antipsychotic and is a dopamine and 5HT2A receptor antagonist with a unique receptor binding profile. As previously mentioned, ziprasidone has a very high 5-HT2A/D2 affinity ratio, binds to multiple serotonin receptors in addition to 5-HT2A, and blocks monoamine transporters preventing 5HT and NE reuptake. On the other hand, ziprasidone has a low affinity for muscarinic cholinergic M1, histamine H1, and alpha1-adrenergic receptors. [A174562] |
| DrugBank MoA: | The effects of ziprasidone are differentiated from other antispychotics based on it's preference and affinity for certain receptors. Ziprasidone binds to serotonin-2A (5-HT2A) and dopamine D2 receptors in a similar fashion to other atypical antipsychotics; however, one key difference is that ziprasidone has a higher 5-HT2A/D2 receptor affinity ratio when compared to other antipsychotics such as olanzapine, quetiapine, risperidone, and aripiprazole.[A363] Ziprasidone offers enhanced modulation of mood, notable negative symptom relief, overall cognitive improvement and reduced motor dysfunction which is linked to it's potent interaction with 5-HT2C, 5-HT1D, and 5-HT1A receptors in brain tissue.[A363] Ziprasidone can bind moderately to norepinephrine and serotonin reuptake sites which may contribute to antidepressant and anxiolytic activity.[A363] Patient's taking ziprasidone will likely experience a lower incidence of orthostatic hypotension, cognitive disturbance, sedation, weight gain, and disruption in prolactin levels since ziprasidone has a lower affinity for histamine H1, muscarinic M1, and alpha1-adrenoceptors.[A363] |
| Targets: | Dopamine D2 receptor; 5-hydroxytryptamine receptor 2A; 5-hydroxytryptamine receptor 1A; 5-hydroxytryptamine receptor 1D; 5-hydroxytryptamine receptor 2C; Dopamine D1 receptor; Dopamine D5 receptor; Dopamine D3 receptor; Dopamine D4 receptor; 5-hydroxytryptamine receptor 1B; 5-hydroxytryptamine receptor 1E; 5-hydroxytryptamine receptor 6; 5-hydroxytryptamine receptor 7; Histamine H1 receptor; Alpha-1A adrenergic receptor; Alpha-1B adrenergic receptor; Alpha-2A adrenergic receptor; Alpha-2B adrenergic receptor; Alpha-2C adrenergic receptor; Muscarinic acetylcholine receptor M1; Muscarinic acetylcholine receptor M2; Muscarinic acetylcholine receptor M3; Muscarinic acetylcholine receptor M4; Muscarinic acetylcholine receptor M5; NA; 5-hydroxytryptamine receptor 5A |
| Inclusion Criteria: |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
|---|
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T03 | Angiotensin-converting enzyme | ACE | INHIBITOR | Target is a single protein chain | P12821 | ACE_HUMAN | Details |
| T06 | Sulfonylurea receptor 1 | ABCC8 | Target is a single protein chain | Q09428 | ABCC8_HUMAN | Details | |
| T15 | Steryl-sulfatase | STS | INHIBITOR | Hydrolase | P08842 | STS_HUMAN | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I02 | 1184 | nephrotic syndrome | "A nephrosis characterized by marked increase in glomerular protein permeability resulting in marked elevation of urine protein levels, hypoalbuminemia, hyperlipidemia, and hypercoagulability." [url:https\://en.wikipedia.org/wiki/Nephrotic_syndrome, url:https\://www.niddk.nih.gov/health-information/kidney-disease/nephrotic-syndrome-adults] | Details |