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Pathway Description
Duloxetine SNRI - Serotonin reuptake Inhibition Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2023-07-10
Last Updated: 2023-11-27
Duloxetine is a serotonin norepinephrine reuptake inhibitor used to treat generalized anxiety disorder, neuropathic pain, osteoarthritis, and stress incontinence. It blocks both sodium dependent serotonin and sodium dependent norepinephrine transporters from removing serotonin and norepinephrine respectively from the synaptic cleft. This allows an accumulation of the neurotransmitters to stimulate their receptors repeatedly increasing the signal of the receptors. In depressed individuals, serotonin and norepinephrine stimulation is low so an increase in serotonin and norepinephrine in the synapses can increase the stimulation of these receptors. The receptors that are being stimulated are 5-HT 2A, 2B, and 2C serotonin receptors and alpha 1 and beta 1 adrenergic receptors. Stimulation of the 2A, 2B and 3C receptor can increase cognitive abilities like learning, appetite, memory, mood and sleep. Sensitization of alpha A1 and beta B1 adrenergic receptors also improve cognitive function, fatigue, sleep and the immune system. In addition to its general SNRI properties, duloxetine also increases dopamine levels, specifically in the prefrontal cortex. Due to the involvement of the prefrontal cortex in depression, the actions of duloxetine in this region also contribute to its efficacy in the treatment of depression. However, the mechanism of action does not involve the inhibition of dopamine transporters. The mechanism of action behind the increase in dopamine levels involves the inhibition of norepinephrine transporters. These transporters have a significant affinity for dopamine, resulting in the transporter’s ability to act on both dopamine and norepinephrine. Therefore, inhibition of norepinephrine transporters can lead to an increase in dopamine. This increase in dopamine specifically occurs in the prefrontal cortex, where dopamine transporters are scarce, and reuptake relies more heavily on norepinephrine transporters. Duloxetine has no significant activity for muscarinic, cholinergic, alpha2-adrenergic, or H1 histaminergic receptors
References
Duloxetine SNRI - Serotonin reuptake Inhibition pathway References
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