Indirect agonists work through varying mechanisms to achieve their effects, including transporter blockade, induction of transmitter release, and inhibition of transmitter breakdown.
Cocaine is a monoamine transporter blocker and, thus, an indirect agonist of dopamine receptors.
Blockage of DAT increases the extracellular concentration of dopamine, therefore increasing the amount of dopamine receptor binding and signaling.
Fenfluramine is an indirect agonist of serotonin receptors.
However, fenfluramine also acts to induce non-exocytotic serotonin release; in a mechanism similar to that of methamphetamine in dopamine neurons, fenfluramine binds to VMAT2, disrupting the compartmentalization of serotonin into vesicles and increasing the concentration of cytoplasmic serotonin available for drug-induced release.