Repositioning Candidate Details
| Candidate ID: | R0153 |
| Source ID: | DB00458 |
| Source Type: | approved |
| Compound Type: | small molecule |
| Compound Name: | Imipramine |
| Synonyms: | 10,11-dihydro-N,N-dimethyl-5H-dibenz[b,f]azepine-5-propanamine; 5-[3-(dimethylamino)propyl]-10,11-dihydro-5H-dibenz[b,f]azepine; Imipramine; Imizine; N-(gamma-Dimethylaminopropyl)iminodibenzyl; N-(γ-dimethylaminopropyl)iminodibenzyl |
| Molecular Formula: | C19H24N2 |
| SMILES: | CN(C)CCCN1C2=CC=CC=C2CCC2=CC=CC=C12 |
| Structure: |
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| DrugBank Description: | Imipramine, the prototypical tricyclic antidepressant (TCA), is a dibenzazepine-derivative 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, imipramine does not affect mood or arousal, but may cause sedation. In depressed individuals, imipramine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Tertiary amine TCAs, such as imipramine and amitriptyline, are more potent inhibitors of serotonin reuptake than secondary amine TCAs, such as nortriptyline and desipramine. 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 . Imipramine has less sedative and anticholinergic effects than the tertiary amine TCAs, amitriptyline and clomipramine. Imipramine may be used to treat depression and nocturnal enuresis in children . Unlabeled indications include chronic and neuropathic pain (including diabetic neuropathy), panic disorder, attention-deficit/hyperactivity disorder (ADHD), and post-traumatic stress disorder (PTSD) . |
| CAS Number: | 50-49-7 |
| Molecular Weight: | 280.4073 |
| DrugBank Indication: | For the relief of symptoms of depression and as temporary adjunctive therapy in reducing enuresis in children aged 6 years and older . May also be used off-label to manage panic disorders with or without agoraphobia, as a second line agent for ADHD in children and adolescents, to manage bulimia nervosa, for short-term management of acute depressive episodes in bipolar disorder and schizophrenia, for the treatment of acute stress disorder and posttraumatic stress disorder, and for symptomatic treatment of postherpetic neuralgia and painful diabetic neuropathy . |
| DrugBank Pharmacology: | Imipramine is a tricyclic antidepressant with general pharmacological properties similar to those of structurally related tricyclic antidepressant drugs such as amitriptyline and doxepin. While it acts to block both, imipramine displays a much higher affinity for the serotonin reuptake transporter than for the norepinephrine reuptake transporter . Imipramine produces effects similar to other monoamine targeting antidepressants, increasing serotonin- and norepinephrine-based neurotransmission. This modulation of neurotransmission produces a complex range of changes in brain structure and function along with an improvement in depressive symptoms. The changes include increases in hippocampal neurogenesis and reduced downregulation of this neurogenesis in response to stress . These implicate brain derived neurotrophic factor signalling as a necessary contributor to antidepressant effect although the link to the direct increase in monoamine neurotransmission is unclear. Serotonin reuptake targeting agents may also produce a down-regulation in β-adrenergic receptors in the brain . |
| DrugBank MoA: | Imipramine works by inhibiting the neuronal reuptake of the neurotransmitters norepinephrine and serotonin . It binds the sodium-dependent serotonin transporter and sodium-dependent norepinephrine transporter reducing the reuptake of norepinephrine and serotonin by neurons. Depression has been linked to a lack of stimulation of the post-synaptic neuron by norepinephrine and serotonin . Slowing the reuptake of these neurotransmitters increases their concentration in the synaptic cleft, producing knock-on effects in protein kinase signalling which is thought to contribute to changes in neurotransmission and brain physiology which relieves symptoms of depression . |
| Targets: | Sodium-dependent noradrenaline transporter inhibitor; 5-hydroxytryptamine receptor 2A antagonist; Sodium-dependent serotonin transporter inhibitor; Histamine H1 receptor antagonist; Alpha-1A adrenergic receptor antagonist; Alpha-1D adrenergic receptor 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; Potassium voltage-gated channel subfamily D member 2 inhibitor; Potassium voltage-gated channel subfamily D member 3 inhibitor; 5-hydroxytryptamine receptor 2C antagonist&binder; Alpha-1B adrenergic receptor antagonist; 5-hydroxytryptamine receptor 7 antagonist; D(1) dopamine receptor binder; Dopamine D2 receptor binder; Potassium voltage-gated channel subfamily H member 2 inhibitor; Sodium-dependent dopamine transporter inhibitor; 5-hydroxytryptamine receptor 1A activator; 5-hydroxytryptamine receptor 6 binder; Potassium voltage-gated channel subfamily H member 1; Alpha-1-acid glycoprotein 2 |
| 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 |