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Pathway Description
Imipramine
Homo sapiens
Drug Metabolism Pathway
Created: 2013-09-11
Last Updated: 2023-06-22
Imipramine is a tricyclic antidepressant that exerts its therapeutic effects by inhibiting norepinephrine and serotonin reuptake in the brain. It does so by competing for the same binding site as norepinephrine on the sodium-dependent noradraneline transporter (SLC6A2) and by competing with serotonin for binding to the sodium-dependent serotonin transporter (SLC6A4). This increases the concentrations of both norepinephrine and serotonin in their respective synapses and reverses the state of low concentrations of both neurotransmitters found in depression. Higher concentrations of norepinephrine and serotonin have also been shown to have long-term neuromodulatory effects. Binding of these neurotransmitters to their respective receptors activate adenylate cyclase, which produces cAMP. cAMP activates protein kinase A which activates cAMP-responsive binding protein 1 (CREB-1). CREB-1 enters the nucleus and affects transcription of brain-derived neurotrophic factor (BDNF). BDNF subsequently stimulates neurogenesis, which may contribute to the long-term reversal of depression. Imipramine is metabolized in the liver mostly through N-demethylation by CYP2C19 into desipramine. Desipramine is an active metabolite and also has similar actions to imipramine on norepinephrine and serotonin reuptake.
References
Imipramine References
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