Melatonin binds primarily to which receptors?

• A. NMDA receptors
• B. MT1 and MT2 receptors
• C. D2 dopamine receptors
• D. GABA-A receptors

Answer: (B)

Melatonin acts mainly through two high-affinity receptors, MT1 and MT2, which are G-protein–coupled receptors abundant in the brain, especially in the suprachiasmatic nucleus—the body's central clock. When melatonin binds these receptors, it modulates circadian signaling and promotes sleep onset by dampening SCN activity and adjusting the timing of the internal clock. This receptor-specific action explains why drugs that mimic melatonin’s effect, like ramelteon, target MT1 and MT2 to improve sleep.

The other receptors listed aren’t the primary melatonin targets: NMDA receptors are excitatory glutamate receptors, D2 receptors are dopamine receptors, and GABA-A receptors are inhibitory chloride channels. Melatonin can influence overall sleep and CNS function indirectly, but its direct, high-affinity actions are through MT1 and MT2.