Repositioning Candidate Details
| Candidate ID: | R0190 |
| Source ID: | DB00557 |
| Source Type: | approved |
| Compound Type: | small molecule |
| Compound Name: | Hydroxyzine |
| Synonyms: | Hychotine; Hydroxine; Hydroxizine; Hydroxizinum; Hydroxycine; Hydroxyzin; Hydroxyzine |
| Molecular Formula: | C21H27ClN2O2 |
| SMILES: | OCCOCCN1CCN(CC1)C(C1=CC=CC=C1)C1=CC=C(Cl)C=C1 |
| Structure: |
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| DrugBank Description: | Hydroxyzine is a first-generation histamine H<sub>1</sub>-receptor antagonist of the dephenylmethane and piperazine classes that exhibits sedative, anxiolytic, and antiemetic properties. It was first developed in 1955, and has since remained a relatively common treatment for allergic conditions such as pruritus, urticaria, dermatoses, and histamine-mediated pruritus. The active metabolite of hydroxyzine, , is also available as an active ingredient in allergic medications, and is responsible for much of its hydroxyzine's antihistaminic effect. Hydroxyzine is also used for generalized anxiety disorder, tension caused by psychoneurosis, and other conditions with manifestations of anxiety. |
| CAS Number: | 68-88-2 |
| Molecular Weight: | 374.904 |
| DrugBank Indication: | Hydroxyzine is indicated for the symptomatic relief of anxiety and tension associated with psychoneuroses, and as an adjunct in organic disease states in which anxiety is manifested. It is also indicated in the treatment of histamine-mediated pruritus and pruritus due to allergic conditions such as chronic urticaria. Canadian labeling states that hydroxyzine is also indicated in adults and children as a premedication prior to medical procedures, such as dental surgery. It is also used in the control of nausea and vomiting, excluding nausea and vomiting of pregnancy. |
| DrugBank Pharmacology: | Hydroxyzine blocks the activity of histamine to relieve allergic symptoms such as pruritus. Activity at off-targets also allows for its use as a sedative anxiolytic and an antiemetic in certain disease states. Hydroxyzine is relatively fast-acting, with an onset of effect that occurs between 15 and 60 minutes and a duration of action between 4-6 hours. Hydroxyzine may potentiate the effects of central nervous system (CNS) depressants following general anesthesia - patients maintained on hydroxyzine should receive reduced doses of any CNS depressants required. Hydroxyzine is reported to prolong the QT/QTc interval based on postmarketing reports of rare events of Torsade de Pointes, cardiac arrest, and sudden death, and should be used with caution in patients with an increased baseline risk for QTc prolongation. |
| DrugBank MoA: | The H<sub>1</sub> histamine receptor is responsible for mediating hypersensitivity and allergic reactions. Exposure to an allergen results in degranulation of mast cells and basophils, which then release histamine and other inflammatory mediators. Histamine binds to, and activates, H<sub>1</sub> receptors, which results in the further release of pro-inflammatory cytokines, such as interleukins, from basophils and mast cells. These downstream effects of histamine binding are responsible for a wide variety of allergic symptoms, such as pruritus, rhinorrhea, and watery eyes. Hydroxyzine is a potent inverse agonist of histamine H<sub>1</sub>-receptors - inverse agonists are agents that are considered to have a "negative efficacy", so rather than simply blocking activity at a receptor they actively dampen its activity. Inverse agonism at these receptors is responsible for hydroxyzine's efficacy in the treatment of histaminic edema, flare, and pruritus. Hydroxyzine is not a cortical depressant, so its sedative properties likely occur at the subcortical level of the CNS. These sedative properties allow activity as an anxiolytic. Antiemetic efficacy is likely secondary to activity at off-targets. |
| Targets: | Histamine H1 receptor inverse agonist; Potassium voltage-gated channel subfamily H member 2 inhibitor |
| Inclusion Criteria: | Therapeutic strategy associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
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