American Board of Internal Medicine (ABIM) Certification Practice Exam

Which neurotransmitter is primarily targeted by duloxetine in the treatment of painful diabetic neuropathy?

1. Dopamine

2. Serotonin

3. Norepinephrine

4. GABA

The correct answer is: Serotonin

Duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI) that is used in the treatment of various conditions, including painful diabetic neuropathy. Its primary mechanism of action involves the inhibition of the reuptake of serotonin and norepinephrine in the synaptic cleft, which enhances the levels of these neurotransmitters in the brain. In the context of painful diabetic neuropathy, while serotonin does play a role in modulating pain perception, the pivotal action of duloxetine also includes significant effects on norepinephrine. The increase in both serotonin and norepinephrine levels contributes to the analgesic effect, but it is important to recognize that the benefit of duloxetine for neuropathic pain stems from this dual action. While dopamine and GABA are important neurotransmitters in the central nervous system, they are not the primary targets of duloxetine in this specific therapeutic context. While dopamine can have a role in reward and motor functions and GABA is primarily an inhibitory neurotransmitter that regulates excitability, they are not directly involved in the mechanism through which duloxetine reduces pain associated with diabetic neuropathy.