Tricyclic antidepressants such as amitriptyline and imipramine primarily function by inhibiting the reuptake of which two main neurotransmitters?

• A. Serotonin and Dopamine
• B. Serotonin and Norepinephrine
• C. Acetylcholine and Dopamine
• D. GABA and Glutamate

Answer: (B)

Tricyclic antidepressants work mainly by blocking the reuptake transporters for serotonin and norepinephrine, increasing their levels in the synapse and enhancing mood-related signaling. Amitriptyline and imipramine inhibit both SERT and NET, giving them a dual action on these two key neurotransmitters. This makes serotonin and norepinephrine the correct pairing. Dopamine reuptake isn’t the primary target of these drugs, and acetylcholine or GABA/glutamate aren’t the monoamines whose reuptake is blocked by TCAs.