Indirect agonists: reuptake inhibitors, enzyme inhibitors and releasers
Explains drugs that never touch the receptor but still boost signaling by raising the neurotransmitter in the cleft: blocking reuptake, blocking breakdown, or forcing release.
Where this fitsConnects to 3 · Unlocks 2
- Connects to
- The synapse: release, binding and termination — Each mechanism changes one step of the synapse you already know.
- Norepinephrine and serotonin — and serotonin syndrome — SSRIs, MAOIs and serotonin syndrome come back as mechanisms.
- Dopamine: receptor families, clearance and pathways — The dopamine synapse is the worked example: every step has a drug.
- Unlocks
- Safety: therapeutic index, dosing across species, allergy and polypharmacy — Stacking these mechanisms (MAOI + MDMA) is the classic dangerous interaction.
- The reward circuit: reinforcement and dopamine — Cocaine and amphetamine raise dopamine in the reward circuit through these mechanisms.
Orient
Indirect agonists raise the amount of endogenous NT in the synapse. Reuptake inhibitor – drug binds to reuptake mechanisms, blocking reuptake resulting in more neurotransmitter in synaptic cleft. Enzyme inhibitor – drug binds to or otherwise deactivates enzymes that break down neurotransmitter. Releasing agent (releaser) – drug stimulates release of neurotransmitter from the pre-synaptic neuron.
Course terms
Your professor's wording, word for word from the slides. Learn the term and this definition — the explanation underneath is only there to help it make sense.
- Reuptake inhibitor
“Drug binds to reuptake mechanisms, blocking reuptake resulting in more neurotransmitter in synaptic cleft”Slides 05, p. 18
SSRIs; cocaine and Ritalin (DA reuptake).
- Indirect agonism
“Antagonizes transporter proteins; indirect agonism through increasing synaptic NT”Slides 05, p. 18
The NT does the work; the drug just raises how much is there.
- Enzyme inhibitor
“Drug binds to or otherwise deactivates enzymes that break down neurotransmitter, resulting in more neurotransmitter in synaptic cleft”Slides 05, p. 20
MAOIs; irreversible AChE inhibitors in venoms.
- Tyramine
“Too much tyramine causes NE release and hypertension”Slides 05, p. 20
Why MAOI users avoid aged/fermented foods.
- Releaser
“Drug stimulates release of neurotransmitter from pre-synaptic neuron”Slides 05, p. 25
Amphetamine/methamphetamine (DA/NE), MDMA (5-HT); risk of depletion, excitotoxicity and oxidative stress.
From your course: Course slides 05, pp. 18–30
Tip: the ← and → keys move through the lesson.
Full lesson: Monoamine transport