A Quiet ADHD Dopamine Synapse
Placeholder: prefrontal dopamine signaling starts low and understimulated in ADHD.
- Full: Vesicular DA stores (placeholder caption)
- Normal uptake: DAT activity (placeholder caption)
- Low: Synaptic DA tone (placeholder caption)
- ~5–7%: ADHD prevalence (placeholder caption)
Storage before stimulation
Placeholder text: dopamine sits packaged in presynaptic vesicles, awaiting a release trigger.
Amphetamine Rides the Transporter Inward
Placeholder: amphetamine is a DAT substrate, entering the neuron via reverse transport.
- DAT substrate: Entry route (placeholder caption)
- ~30–60 min: Onset (oral IR) (placeholder caption)
- High: Lipophilicity (placeholder caption)
- Beginning: Transporter reversal (placeholder caption)
Substrate, not just blocker
Placeholder text: unlike methylphenidate, amphetamine is carried through DAT into the cell.
Vesicles Lose Their Dopamine Grip
Placeholder: amphetamine disrupts the vesicular pH gradient, dopamine leaks out.
- Present: VMAT2 disruption (placeholder caption)
- Rising: Cytoplasmic DA (placeholder caption)
- Collapsing: Vesicle pH gradient (placeholder caption)
- Releasing agent: Mechanism class (placeholder caption)
From vesicle to cytoplasm
Placeholder text: stored dopamine redistributes into the cytoplasmic pool, primed for efflux.
Placeholder highlight: this vesicular step is unique to amphetamine, not methylphenidate.
DAT Flips — Active Efflux Begins
Placeholder: the transporter reverses, actively pumping dopamine into the synapse.
- Reversed: DAT direction (placeholder caption)
- Active transport: Efflux mechanism (placeholder caption)
- Partial, also present: Reuptake blockade (placeholder caption)
- Dual release + block: Net effect (placeholder caption)
Dual mechanism in action
Placeholder text: efflux plus blockade together push more dopamine into the cleft.
A Larger Surge Than Reuptake Inhibition Alone
Placeholder: combined release and blockade out-perform blockade-only stimulants.
- ~2×: Surge vs. methylphenidate (placeholder caption)
- Up to 12–14h: Duration (Vyvanse) (placeholder caption)
- Release + block: Mechanism summary (placeholder caption)
- Stronger effect size: Clinical relevance (placeholder caption)
Why amphetamine feels stronger
Placeholder text: dual-action release plus blockade generally produces a bigger dopamine surge.
Placeholder highlight: prodrug formulations like Vyvanse smooth this surge over time.