A Comprehensive Monograph on Dextroamphetamine (DB01576)

Section 1: Introduction and Executive Summary

1.1 Overview

Dextroamphetamine is a potent small molecule drug, identified as the dextrorotatory, or (S)-enantiomer, of amphetamine. It is classified pharmacologically as a central nervous system (CNS) stimulant and a non-catecholamine sympathomimetic amine.[1] As a cornerstone therapy in the management of specific neurobehavioral disorders, its clinical utility is well-established, though it is invariably accompanied by a complex and significant risk profile that necessitates careful clinical management.

1.2 Therapeutic Indications

The United States Food and Drug Administration (FDA) has approved dextroamphetamine for two primary indications: Attention Deficit Hyperactivity Disorder (ADHD) and narcolepsy.[1] In the treatment of ADHD, dextroamphetamine functions to increase attention and decrease restlessness and impulsivity in children and adults who are overactive, easily distracted, or cannot concentrate for extended periods. It is critical to recognize that pharmacotherapy with dextroamphetamine is not a standalone treatment but is indicated as an integral component of a comprehensive therapeutic program that includes psychological, educational, and social interventions.[5] For narcolepsy, it is used to manage the primary symptom of uncontrollable daytime sleepiness.[2]

1.3 Pharmacological Synopsis

The therapeutic and psychoactive effects of dextroamphetamine are mediated primarily through its potent activity on catecholaminergic neurotransmitter systems. Its fundamental mechanism of action involves increasing the synaptic concentrations of dopamine and norepinephrine in the brain, particularly within the striatum and prefrontal cortex.[3] This is achieved through a multifaceted process involving the inhibition and reversal of transporter proteins, disruption of vesicular storage, and inhibition of enzymatic degradation.