Indirectacting

Indirectacting refers to pharmacological agents whose effects arise not from directly binding and activating receptors, but from altering the availability or action of endogenous neurotransmitters. In practice, indirect-acting drugs increase transmitter activity by promoting release, blocking reuptake, or inhibiting enzymatic breakdown, thereby amplifying signaling at receptors.

Mechanisms fall into several related categories. Some agents stimulate the release of endogenous transmitters from nerve terminals, a common feature of indirect-acting sympathomimetics such as amphetamine and methamphetamine. Others inhibit uptake, increasing synaptic concentrations of neurotransmitters; examples include cocaine and certain methylphenidate-like drugs. Another important group comprises cholinesterase inhibitors (for example physostigmine, neostigmine, and donepezil), which raise acetylcholine levels by slowing its breakdown, thus enhancing cholinergic signaling without directly activating receptors. Some drugs combine both direct and indirect actions, and there are agents with mixed indirect effects across different neurotransmitter systems.

Clinical use and considerations vary by mechanism. Indirect-acting stimulants are used in conditions such as attention-deficit/hyperactivity disorder and certain sleep disorders but carry risks of cardiovascular effects and potential misuse. Indirect-acting cholinesterase inhibitors are employed in myasthenia gravis and some forms of dementia, with therapy tailored to balance symptom relief against adverse effects from excess cholinergic activity. The term distinguishes these agents from direct-acting receptor agonists, emphasizing that their pharmacologic impact depends on endogenous transmitter dynamics. See also: adrenergic agents, cholinesterase inhibitors.