Multiple endogenous receptors via released ligands

Multiple endogenous receptors via released ligands refers to a pharmacological mechanism where a drug acts indirectly by triggering the release of endogenous signaling molecules, such as neurotransmitters or hormones, from their storage sites. Instead of binding directly to a receptor, these agents—often called indirect agonists or secretagogues—increase the extracellular concentration of natural ligands like norepinephrine, dopamine, or serotonin, which then activate their respective receptor populations [1][2]. This mechanism is prominently seen in indirectly acting sympathomimetic drugs used to treat conditions like ADHD, narcolepsy, and certain types of hypotension [1]. Because the released ligands can act on a wide variety of receptor subtypes (e.g., alpha and beta-adrenergic receptors), the physiological response is often broad and systemic [2]. However, this lack of specificity can lead to significant safety concerns, including cardiovascular strain, potential for abuse, and tachyphylaxis, where the depletion of endogenous ligand stores results in a rapidly diminishing therapeutic effect [1][3].

Other names

Indirectly acting agonistsLigand releasersSecretagoguesIndirect sympathomimetics

Induction of endogenous ligand release from storage vesicles or cytoplasm into the extracellular space, where they activate their respective receptors [1][2].