Lisdexamfetamine - Mechanism of Action

Mechanism of Action

Because lisdexamphetamine is active in the human brain as amphetamine, its mechanism of action is identical to the mechanism of action of amphetamine.

Although the precise mechanism of action by which amphetamines improve the symptoms of ADHD remains unknown, they are thought to block the reuptake of norepinephrine (noradrenaline) and dopamine into the presynaptic neuron and increase their availability into the extraneuronal space.

Lisdexamfetamine (LDX) is a therapeutically inactive molecule. After oral ingestion, LDX is broken down by enzymes to l-lysine, a naturally occurring essential amino acid, and active d-amphetamine, which is responsible for the drug’s activity. The conversion of LDX to d-amphetamine is not affected by gastrointestinal pH and is unlikely to be affected by alterations in normal gastrointestinal transit times. LDX was developed with the goal of providing a long duration of effect that is consistent throughout the day, with reduced potential for abuse-related liking. The attachment of the amino acid lysine slows down the relative amount of d-amphetamine available to the blood stream. Because no free d-amphetamine is present in LDX capsules, d-amphetamine does not become available through mechanical manipulation, such as crushing or simple extraction. A relatively sophisticated biochemical process is needed to obtain d-amphetamine from LDX.

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