How Procentra Works for ADHD
Procentra (dextroamphetamine) works by binding to dopamine and norepinephrine transporters in the brain's striatum, increasing synaptic concentrations of these neurotransmitters, which enhances prefrontal cortex function and improves executive control, attention, and impulse regulation in patients with ADHD. 1
Mechanism of Action
Primary Neurotransmitter Effects:
- Dextroamphetamine acts as a substrate for cellular monoamine transporters, particularly the dopamine transporter (DAT) and to a lesser extent the norepinephrine transporter (NET) 2
- The medication increases extracellular dopamine and norepinephrine in the synaptic cleft through acute administration 1
- This enhancement of dopamine and norepinephrine optimizes prefrontal cortex activity, which controls executive functions including planning, impulse control, working memory, and attention 1
Targeted Brain Regions:
- The primary site of action is the striatum, where stimulants bind to dopamine transporters 1
- The prefrontal cortex receives enhanced neurotransmitter signaling, ameliorating deficits in inhibitory control and working memory characteristic of ADHD 1
- PET scanning studies demonstrate that untreated adults with ADHD show 8.1% lower cerebral glucose metabolism than controls, with greatest differences in the superior prefrontal cortex and premotor areas 1
Clinical Pharmacology
Absorption and Onset:
- Dextroamphetamine is rapidly absorbed from the gastrointestinal tract and begins acting within 30 minutes after oral ingestion 1
- Effects on behavior appear during the absorption phase, beginning 30 minutes after ingestion 1
- The medication demonstrates low plasma protein binding and rapid extracellular metabolism 1
Duration and Metabolism:
- The plasma half-life of dextroamphetamine ranges approximately 11 hours, longer than methylphenidate's 3-hour half-life 1
- Up to 80% may be excreted unchanged in the urine 1
- Multiple pathways are involved in metabolism, including p-hydroxylation, N-demethylation, deamination, and conjugation 1
Therapeutic Effects
Efficacy Profile:
- Stimulants demonstrate a 70% response rate when a single stimulant is tried in controlled studies involving more than 5,000 school-age children 1
- Effect sizes for changes in behavior or attention in short-term trials range from 0.8 to 1.0 standard deviations on teacher reports 1
- In adults with ADHD, dextroamphetamine at appropriate doses (approximately 1 mg/kg total daily dose) shows 78% improvement versus 4% placebo response 1
Symptom Improvements:
- Dextroamphetamine improves the most salient and impairing behavioral symptoms of ADHD, including overt aggression, when medication is taken 1
- The medication enhances executive control processes in the prefrontal cortex, reducing deficits in inhibitory control and working memory 1
- Studies demonstrate improvements in both ADHD symptoms and associated conditions compared with placebo 1
FDA-Approved Indications
Procentra is FDA-approved for:
- Narcolepsy 3
- Attention Deficit Disorder with Hyperactivity as part of a total treatment program in pediatric patients ages 3 to 16 years 3
- The diagnosis should address moderate to severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity 3
Important Clinical Considerations
Mechanism Limitations:
- Although psychostimulants are medications of choice for ADHD treatment, their central mechanisms of action remain incompletely understood 1
- No consistent changes in cerebral glucose metabolism were found in PET scans before and during medication in adults with ADHD, even though adults showed significant behavioral improvements 1
- Whether compensatory mechanisms occur after slower oral absorption is not known 1
Non-Specific Effects:
- Stimulant medications improve behavior and attention in children with other disorders and in normal subjects, so these drug effects are neither "paradoxical" nor specific for ADHD 1
- A positive response to stimulants is not diagnostic for ADHD 1
Dosing Considerations: