What differentiates an indirect agonist from a direct agonist?

An indirect agonist is characterized by its ability to promote the effects of a neurotransmitter without directly binding to the same site as the natural ligand. This means that while it does not interact with the receptor in the same way that a direct agonist does, it can still enhance the overall activity of the neurotransmitter by altering its availability or efficacy in the synaptic cleft. For example, an indirect agonist might increase the release of neurotransmitters or inhibit their reuptake, thus enhancing their action without directly occupying the receptor site itself.

In contrast, a direct agonist binds to the receptor itself and mimics the action of the natural ligand, establishing a clear interaction at the binding site. Therefore, the role of an indirect agonist distinctly involves modification of the neurotransmitter's action without direct receptor engagement, which aligns with the understanding provided by the correct choice.