Lisdexamfetamine dimesylate

Elia, Josephine; Easley, Chris; Kirkpatrick, Peter

doi:10.1038/nrd2315

Cited by 13 publications

(8 citation statements)

References 11 publications

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“…29 An example of recent amide prodrugs in clinical use is lisdextroamfetamine (Vyvanse, New River Pharmaceuticals/Shire). 30 Consequently, amide derivation is a valuable alternative for esterification in the tissue targeting by the prodrug approach.…”

Section: ' Results and Discussionmentioning

confidence: 99%

Large Amino Acid Transporter 1 (LAT1) Prodrugs of Valproic Acid: New Prodrug Design Ideas for Central Nervous System Delivery

et al. 2011

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Central nervous system (CNS) drug delivery is a major challenge in drug development because the blood-brain barrier (BBB) efficiently restricts the entry of drug molecules into the CNS at sufficient amounts. The brain uptake of poorly penetrating drugs could be improved by utilizing the transporters at the BBB with a prodrug approach. In this study, we designed four phenylalanine derivatives of valproic acid and studied their ability to utilize a large amino acid transporter 1 (LAT1) in CNS delivery with an aim to show that the meta-substituted phenylalanine prodrugs bind to LAT1 with a higher affinity compared with the affinity of the para-substituted derivatives. All of the prodrugs crossed the BBB carrier mediatedly via LAT1 in in situ rat brain perfusion. For the first time, we introduced a novel meta-substituted phenylalanine analogue promoiety which improved the LAT1 affinity 10-fold and more importantly the rat brain uptake of the prodrug 2-fold compared with those of the para-substituted derivatives. Therefore, we have characterized a new prodrug design idea for CNS drug delivery utilizing a transporter-mediated prodrug approach.

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Section: ' Results and Discussionmentioning

confidence: 99%

Large Amino Acid Transporter 1 (LAT1) Prodrugs of Valproic Acid: New Prodrug Design Ideas for Central Nervous System Delivery

et al. 2011

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“…69 New River Pharmaceuticals designed an amphetamine prodrug, lisdexamfetamine (VyvanseÔ, NRP104) 14, which is converted to D-amphetamine 15 in the gastrointestinal tract after oral administration and, as a consequence, has reduced abuse potential. [69][70][71] In February 2007, New River and Shire Pharmaceuticals obtained FDA approval for the use of lisdexamfetamine 14 to help treat ADHD, and in April 2007 Shire bought New River.…”

Section: Np-derived Drugs Approved From 2005 To 2007mentioning

confidence: 99%

Natural products to drugs: natural product-derived compounds in clinical trials

2008

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Natural product and natural product-derived compounds that are being evaluated in clinical trials or are in registration (as at 31st December 2007) have been reviewed, as well as natural product-derived compounds for which clinical trials have been halted or discontinued since 2005. Also discussed are natural product-derived drugs launched since 2005, new natural product templates and late-stage development candidates.

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“…Conversion of LDX to its active component requires enzymatic hydrolysis that results in a slow rise in serum d -amphetamine level, which possibly provides a reduced potential for abuse 54 . In a human abuse-liability study involving individuals with a history of drug abuse, lisdexamfetamine produced subjective responses that were significantly less than an equivalent oral dose of d -amphetamine immediate release 55 . Modafinil and armodafinil seem to act mostly at the suprachiasmatic nucleus in the hypothalamus and at the amygdala, both regions primarily involved in wakefulness.…”

Section: Discussionmentioning

confidence: 99%

“…54 In a human abuse-liability study involving individuals with a history of drug abuse, lisdexamfetamine produced subjective responses that were significantly less than an equivalent oral dose of d-amphetamine immediate release. 55 Modafinil and armodafinil seem to act mostly at the suprachiasmatic nucleus in the hypothalamus and at the amygdala, both regions primarily involved in wakefulness. So, their interaction with the nucleus accumbens is believed to be less relevant than that of the amphetamines, hence allowing them to bear reduced addictive potential.…”

Section: Cns Spectrumsmentioning

confidence: 99%

Adjunctive treatment with psychostimulants and stimulant-like drugs for resistant bipolar depression: a systematic review and meta-analysis

Tsapakis¹,

Preti

Mintzas³

et al. 2020

CNS Spectr.

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Background Depression is considered to be the most difficult to treat phase of bipolar disorder as patients experience residual symptoms causing long-term disability. This work aims to explore the role of add-on stimulant and stimulant-like medication in resistant bipolar depression patients. Methods Systematic review of add-on stimulants and stimulant-like drugs in resistant bipolar depression by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Analysis was performed using the random-effects models. Heterogeneity was evaluated with Cochran’s Q and I2 statistics. Results Six randomized controlled trials of add-on modafinil, armodafinil, and lisdexamphetamine (LDX) (n = 813) vs placebo (n = 815) in the treatment of resistant bipolar depression were included. These drugs were more likely to induce remission from an episode of resistant bipolar depression (relative risk [RR] = 1.37; 95% confidence interval [CI]: 1.06-1.77; number needed to treat for an additional beneficial outcome = 16). Moreover, they did not induce more dropouts than placebo (RR = 1.04; 95% CI: 0.91-1.18), nor did they increase the risk of adverse effects (53/772 vs 41/771) at the end of treatment (RR = 1.30; 95% CI: 0.81-2.10; number needed to treat for an additional harmful outcome = 62). Suicidality and manic switch were not affected by active treatment. Heterogeneity was low (Cochran’s Q: P > .05), but sometimes with a large CI. Conclusions LDX, modafinil, and armodafinil seem to offer a reasonably well-tolerated and safe treatment in resistant bipolar depression. Treatment guidelines should, therefore, be revised to include these medications earlier in the therapeutic algorithm for resistant acute bipolar depression. Further research is, however, necessary for the elucidation of the clinical usefulness of these and other similar compounds.

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Lisdexamfetamine dimesylate

Cited by 13 publications

References 11 publications

Large Amino Acid Transporter 1 (LAT1) Prodrugs of Valproic Acid: New Prodrug Design Ideas for Central Nervous System Delivery

Large Amino Acid Transporter 1 (LAT1) Prodrugs of Valproic Acid: New Prodrug Design Ideas for Central Nervous System Delivery

Natural products to drugs: natural product-derived compounds in clinical trials

Adjunctive treatment with psychostimulants and stimulant-like drugs for resistant bipolar depression: a systematic review and meta-analysis

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