Repositioning Candidate Details
| Candidate ID: | R0097 |
| Source ID: | DB00363 |
| Source Type: | approved |
| Compound Type: | small molecule |
| Compound Name: | Clozapine |
| Synonyms: | |
| Molecular Formula: | C18H19ClN4 |
| SMILES: | CN1CCN(CC1)C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 |
| Structure: |
|
| DrugBank Description: | A tricyclic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. |
| CAS Number: | 5786-21-0 |
| Molecular Weight: | 326.823 |
| DrugBank Indication: | For use in patients with treatment-resistant schizophrenia. |
| DrugBank Pharmacology: | Clozapine is a psychotropic agent belonging to the chemical class of benzisoxazole derivatives and is indicated for the treatment of schizophrenia. Clozapine is a selective monoaminergic antagonist with high affinity for the serotonin Type 2 (5HT<sub>2</sub>), dopamine Type 2 (D2), 1 and 2 adrenergic, and H1 histaminergic receptors. Clozapine acts as an antagonist at other receptors, but with lower potency. Antagonism at receptors other than dopamine and 5HT<sub>2</sub> with similar receptor affinities may explain some of the other therapeutic and side effects of Clozapine. Clozapine's antagonism of muscarinic M1-5 receptors may explain its anticholinergic effects. Clozapine's antagonism of histamine H1 receptors may explain the somnolence observed with this drug. Clozapine's antagonism of adrenergic a1 receptors may explain the orthostatic hypotension observed with this drug. |
| DrugBank MoA: | Clozapine's antipsychotic action is likely mediated through a combination of antogistic effects at D2 receptors in the mesolimbic pathway and 5-HT2A receptors in the frontal cortex. D2 antagonism relieves positive symptoms while 5-HT2A antagonism alleviates negative symptoms. |
| Targets: | Dopamine D1 receptor; Dopamine D2 receptor; Dopamine D3 receptor; Dopamine D4 receptor; Dopamine D5 receptor; 5-hydroxytryptamine receptor 1A; 5-hydroxytryptamine receptor 1B; 5-hydroxytryptamine receptor 1D; 5-hydroxytryptamine receptor 1E; 5-hydroxytryptamine receptor 2A; 5-hydroxytryptamine receptor 3A; 5-hydroxytryptamine receptor 2C; 5-hydroxytryptamine receptor 6; 5-hydroxytryptamine receptor 7; Alpha-2C adrenergic receptor; Histamine H1 receptor; Histamine H4 receptor; Alpha-1A adrenergic receptor; Alpha-1B adrenergic receptor; Alpha-2A adrenergic receptor; Alpha-2B adrenergic receptor; Muscarinic acetylcholine receptor M1; Muscarinic acetylcholine receptor M2; Muscarinic acetylcholine receptor M3; Muscarinic acetylcholine receptor M4; Muscarinic acetylcholine receptor M5; Neuron-specific vesicular protein calcyon; Glutathione S-transferase P; Gamma-aminobutyric acid type B receptor subunit 1; Gamma-aminobutyric acid type B receptor subunit 2; Gamma-aminobutyric acid receptor subunit alpha-1; Gamma-aminobutyric acid receptor subunit beta-1; Gamma-aminobutyric acid receptor subunit gamma-1 |
| Inclusion Criteria: |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
|---|
| 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 |