Serotonin-releasing agents

Name: Sulfonamide-derived drugs (non-antibacterial)
Creator: Jason Cafer, MD

Drugs that reverse the serotonin transporter and release serotonin, rather than blocking its reuptake — the amphetamines, MDMA, mephedrone, methamphetamine and fenfluramine
Releasers act faster and harder than reuptake blockers; the same is true of their toxicity
Serotonin toxicity with an MAOI is the potentially fatal combination; the amphetamines also release norepinephrine, so the pressor reaction rides along
Fenfluramine’s 5-HT2B agonism is the valvulopathy mechanism that withdrew it as an anorectic; the orphan antiseizure product carries echocardiographic monitoring

Class at a glance

Drugs that reverse the serotonin transporter and release serotonin, rather than blocking its reuptake — the amphetamines, MDMA, mephedrone, methamphetamine and fenfluramine
Releasers act faster and harder than reuptake blockers; the same is true of their toxicity

Serotonin toxicity with an MAOI is the potentially fatal combination; the amphetamines also release norepinephrine, so the pressor reaction rides along
Fenfluramine’s 5-HT2B agonism is the valvulopathy mechanism that withdrew it as an anorectic; the orphan antiseizure product carries echocardiographic monitoring

How does a releaser differ from a reuptake inhibitor at the transporter?
A releaser is carried in and reverses the transporter, pumping serotonin out; a reuptake inhibitor only blocks the inward pump.