Serdexmethylphenidate (Azstarys)

Overview

Serdexmethylphenidate is a prodrug of the CNS stimulant dexmethylphenidate used as a first-line treatment for Attention Deficit Hyperactivity Disorder (ADHD).

Mechanism of Action

Attention Deficit Hyperactivity Disorder (ADHD) is an early-onset neurodevelopmental disorder that often extends into adulthood and is characterized by developmentally inappropriate and impaired attention, impulsivity, and motor hyperactivity. Proper diagnosis is hindered by a lack of biological markers (based on symptoms alone), a spectrum of severity, and frequent comorbidities such as autism spectrum disorder, reading disabilities, developmental coordination disorders, and tic disorders. Although the underlying cause(s) is unclear, dopaminergic, noradrenergic, serotonergic, cholinergic, glutaminergic, and opioid neurotransmission likely plays a role. Serdexmethylphenidate is a prodrug of the CNS stimulant dexmethylphenidate(MPH), a common first-line treatment for ADHD. The main effect of MPH is to increase the extracellular levels of dopamine and norepinephrine, which has numerous potential downstream effects. This occurs mainly due to MPH's ability to inhibit the corresponding dopamine and norepinephrine monoamine transporters. Other studies have suggested additional possible MPH functions, including serotonin 5-HT1A receptor agonism, redistribution of vesicular monoamine transporter-2 (VMAT-2), and either direct or indirect activation of α2-adrenergic receptors. Overall, imaging studies reveal that MPH acts to alter brain activity in relevant regions associated with executive function, emotional regulation, reward processing, and working memory.

Indications

Serdexmethylphenidate is a prodrug of dexmethylphenidate that is indicated in combination with dexmethylphenidate for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients aged six years and older.

• Attention Deficit Hyperactivity Disorder (ADHD)