Repositioning Candidate Details
| Candidate ID: | R0427 |
| Source ID: | DB01151 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Desipramine |
| Synonyms: | 5-(gamma-methylaminopropyl)iminodibenzyl; 5-(γ-methylaminopropyl)iminodibenzyl; Desipramine; Desmethylimipramine; DMI; Monodemethylimipramine; N-(3-methylaminopropyl)iminobibenzyl; Norimipramine |
| Molecular Formula: | C18H22N2 |
| SMILES: | CNCCCN1C2=CC=CC=C2CCC2=CC=CC=C12 |
| Structure: |
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| DrugBank Description: | Desipramine hydrochloride is a dibenzazepine-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, desipramine does not affect mood or arousal, but may cause sedation. In depressed individuals, desipramine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Secondary amine TCAs, such as desipramine and nortriptyline, are more potent inhibitors of norepinephrine reuptake than tertiary amine TCAs, such as amitriptyline and doxepine. TCAs also down-regulate cerebral cortical β-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine-H<sub>1</sub> receptors, α<sub>1</sub>-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. See toxicity section below for a complete listing of side effects. Desipramine exerts less anticholinergic and sedative side effects compared to tertiary amine TCAs, such as amitriptyline and clomipramine. Desipramine may be used to treat depression, neuropathic pain (unlabeled use), agitation and insomnia (unlabeled use) and attention-deficit hyperactivity disorder (unlabeled use). |
| CAS Number: | 50-47-5 |
| Molecular Weight: | 266.3807 |
| DrugBank Indication: | For relief of symptoms in various depressive syndromes, especially endogenous depression. It has also been used to manage chronic peripheral neuropathic pain, as a second line agent for the management of anxiety disorders (e.g. panic disorder, generalized anxiety disorder), and as a second or third line agent in the ADHD management. |
| DrugBank Pharmacology: | Desipramine, a secondary amine tricyclic antidepressant, is structurally related to both the skeletal muscle relaxant cyclobenzaprine and the thioxanthene antipsychotics such as thiothixene. It is the active metabolite of imipramine, a tertiary amine TCA. The acute effects of desipramine include inhibition of noradrenaline re-uptake at noradrenergic nerve endings and inhibition of serotonin (5-hydroxy tryptamine, 5HT) re-uptake at the serotoninergic nerve endings in the central nervous system. Desipramine exhibits greater noradrenergic re-uptake inhibition compared to the tertiary amine TCA imipramine. In addition to inhibiting neurotransmitter re-uptake, desipramine down-regulates beta-adrenergic receptors in the cerebral cortex and sensitizes serotonergic receptors with chronic use. The overall effect is increased serotonergic transmission. Antidepressant effects are typically observed 2 - 4 weeks following the onset of therapy though some patients may require up to 8 weeks of therapy prior to symptom improvement. Patients experiencing more severe depressive episodes may respond quicker than those with mild depressive symptoms. |
| DrugBank MoA: | Desipramine is a tricyclic antidepressant (TCA) that selectively blocks reuptake of norepinephrine (noradrenaline) from the neuronal synapse. It also inhibits serotonin reuptake, but to a lesser extent compared to tertiary amine TCAs such as imipramine. Inhibition of neurotransmitter reuptake increases stimulation of the post-synaptic neuron. Chronic use of desipramine also leads to down-regulation of beta-adrenergic receptors in the cerebral cortex and sensitization of serotonergic receptors. An overall increase in serotonergic transmission likely confers desipramine its antidepressant effects. Desipramine also possesses minor anticholinergic activity, through its affinity for muscarinic receptors. TCAs are believed to act by restoring normal levels of neurotransmitters via synaptic reuptake inhibition and by increasing serotonergic neurotransmission via serotonergic receptor sensitization in the central nervous system. |
| Targets: | Sodium-dependent noradrenaline transporter inhibitor; Beta-2 adrenergic receptor antagonist; Sodium-dependent serotonin transporter inhibitor; 5-hydroxytryptamine receptor 2A antagonist; Beta-1 adrenergic receptor other; Sphingomyelin phosphodiesterase inhibitor; Histamine H1 receptor antagonist; Alpha-1 adrenergic receptors antagonist; Muscarinic acetylcholine receptor M1 antagonist; Muscarinic acetylcholine receptor M2 antagonist; Muscarinic acetylcholine receptor M3 antagonist; Muscarinic acetylcholine receptor M4 antagonist; Muscarinic acetylcholine receptor M5 antagonist; 5-hydroxytryptamine receptor 1A binder; 5-hydroxytryptamine receptor 2C binder; Dopamine D2 receptor binder; Alpha-2 adrenergic receptors binder |
| Inclusion Criteria: | Indication associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I17 | 1596 | Mental depression | Mental depression | disease of mental health/ cognitive disorder/ mood disorder | Details |
| I11 | 5295 | Intestinal disease | A gastrointestinal system disease that is located_in the intestine. http://en.wikipedia.org/wiki/Human_gastrointestinal_tract | disease of anatomical entity/gastrointestinal system disease | Details |