Lisdexamfetamine Dimesylate

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Cat Number

API0232126

CAS Number

608137-33-3

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CAS Number

608137-33-3

Synonyms

Lisdexamfetamine mesilate; NRP104; SPD489

Molecular Formula

C17H33N3O7S2

Molecular Weight

455.59

Smiles

CS(O)(=O)=O.CS(O)(=O)=O.CC@@HNC(=O)C@@HCCCCN

General Description

Lisdexamfetamine dimesylate is a central nervous system stimulant and the first chemically formulated prodrug stimulant approved for therapeutic use. It is available as capsules and chewable tablets in various strengths for oral administration and is classified as a Schedule II controlled substance due to its high potential for abuse and dependence.

Mechanism of Action

Lisdexamfetamine is a therapeutically inactive prodrug that undergoes enzymatic hydrolysis in the blood to convert to its active metabolite, dextroamphetamine. Dextroamphetamine blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and increases the release of these monoamines into the extraneuronal space . It achieves this by inhibiting dopamine and norepinephrine transporters, ultimately increasing catecholamine availability in the brain to improve attention and impulse control.

Application

Lisdexamfetamine dimesylate is FDA-approved for the treatment of attention-deficit/hyperactivity disorder in adults and pediatric patients six years and older, and for moderate to severe binge eating disorder in adults. The typical starting dose is 30 mg once daily in the morning, titrated up to a maximum of 70 mg daily as needed. Due to its abuse potential, therapy requires careful patient selection and monitoring for signs of misuse, dependence, and cardiovascular effects.

Ermer JC, et al. described the pharmacokinetic and pharmacodynamic characteristics of lisdexamfetamine dimesylate (LDX), a long-acting d-amphetamine prodrug used for attention-deficit/hyperactivity disorder (ADHD). Following oral administration, LDX is hydrolyzed in the blood to active d-amphetamine, producing a pharmacokinetic profile characterized by a lower peak concentration, delayed time to maximum concentration, and reduced inter- and intra-individual variability compared with immediate-release amphetamine. The therapeutic effect extends up to 13–14 hours post-dose, a duration exceeding that of other long-acting formulations.

Fig. 1 Chemical structure of LDX and immediate metabolites. (Ermer JC, et al., 2016)

References

Ermer JC, et al. Lisdexamfetamine Dimesylate: Prodrug Delivery, Amphetamine Exposure and Duration of Efficacy. Clin Drug Investig. 2016;36(5):341-356.

Schein J, et al. reported a comparative study using matching-adjusted indirect comparison, which incorporated patient-level data from centanafadine trials and published aggregate data from comparator trials to assess safety and efficacy in adults with ADHD. After matching baseline characteristics, centanafadine demonstrated significantly better short-term safety profiles than all comparators, with lower risks of multiple adverse events including decreased appetite, dry mouth, insomnia, and nausea. Efficacy, measured as reduction in ADHD symptom scores, was significantly lower than that of lisdexamfetamine but comparable (non-inferior) to atomoxetine and viloxazine ER.

Fig. 2 Comparisons of safety and efficacy between centanafadine and lisdexamfetamine. (Schein J, et al, 2024)

References

Schein J, et al. Assessment of centanafadine in adults with attention-deficit/hyperactivity disorder: A matching-adjusted indirect comparison vs lisdexamfetamine dimesylate, atomoxetine hydrochloride, and viloxazine extended-release. J Manag Care Spec Pharm. 2024;30(6):528-540.

Does Lisdexamfetamine Dimesylate require refrigeration during storage?

No, it is stable at controlled room temperature (15-25°C). Refrigeration is not required but may be used if humidity is strictly controlled, as it can absorb moisture.

Is Lisdexamfetamine Dimesylate sensitive to acidic or alkaline conditions during handling?

Yes, as a prodrug, its amide bond can hydrolyze under extreme pH conditions. It should be stored in its original, well-closed container away from acidic or basic fumes.

What documentation is required for international shipping of this controlled substance?

We provide all necessary export permits, DEA declarations, and certificates of analysis to facilitate customs clearance in compliance with international narcotics control treaties.

How is the dimesylate salt form confirmed during quality control?

The counterion content is verified using ion chromatography, ensuring the correct stoichiometric ratio of lisdexamfetamine to dimesylate for consistent bioavailability.