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Journal of Psychopharmacology (Oxford,... Jun 2013Amphetamine was discovered over 100 years ago. Since then, it has transformed from a drug that was freely available without prescription as a panacea for a broad range... (Review)
Review
Amphetamine was discovered over 100 years ago. Since then, it has transformed from a drug that was freely available without prescription as a panacea for a broad range of disorders into a highly restricted Controlled Drug with therapeutic applications restricted to attention deficit hyperactivity disorder (ADHD) and narcolepsy. This review describes the relationship between chemical structure and pharmacology of amphetamine and its congeners. Amphetamine's diverse pharmacological actions translate not only into therapeutic efficacy, but also into the production of adverse events and liability for recreational abuse. Accordingly, the balance of benefit/risk is the key challenge for its clinical use. The review charts advances in pharmaceutical development from the introduction of once-daily formulations of amphetamine through to lisdexamfetamine, which is the first d-amphetamine prodrug approved for the management of ADHD in children, adolescents and adults. The unusual metabolic route for lisdexamfetamine to deliver d-amphetamine makes an important contribution to its pharmacology. How lisdexamfetamine's distinctive pharmacokinetic/pharmacodynamic profile translates into sustained efficacy as a treatment for ADHD and its reduced potential for recreational abuse is also discussed.
Topics: Adolescent; Adult; Amphetamine; Amphetamine-Related Disorders; Animals; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Drug Design; Humans; Lisdexamfetamine Dimesylate; Narcolepsy; Prodrugs
PubMed: 23539642
DOI: 10.1177/0269881113482532 -
The New England Journal of Medicine Jul 1977
Clinical Trial
Topics: Analgesics; Clinical Trials as Topic; Dextroamphetamine; Humans; Morphine; Pain, Postoperative
PubMed: 325410
DOI: 10.1056/NEJM197707142970218 -
CNS Drugs Jun 2014Here we review the safety and tolerability profile of lisdexamfetamine dimesylate (LDX), the first long-acting prodrug stimulant for the treatment of... (Review)
Review
BACKGROUND
Here we review the safety and tolerability profile of lisdexamfetamine dimesylate (LDX), the first long-acting prodrug stimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD).
METHODS
A PubMed search was conducted for English-language articles published up to 16 September 2013 using the following search terms: (lisdexamfetamine OR lisdexamphetamine OR SPD489 OR Vyvanse OR Venvanse OR NRP104 NOT review [publication type]).
RESULTS
In short-term, parallel-group, placebo-controlled, phase III trials, treatment-emergent adverse events (TEAEs) in children, adolescents, and adults receiving LDX were typical for those reported for stimulants in general. Decreased appetite was reported by 25-39 % of patients and insomnia by 11-19 %. The most frequently reported TEAEs in long-term studies were similar to those reported in the short-term trials. Most TEAEs were mild or moderate in severity. Literature relating to four specific safety concerns associated with stimulant medications was evaluated in detail in patients receiving LDX. Gains in weight, height, and body mass index were smaller in children and adolescents receiving LDX than in placebo controls or untreated norms. Insomnia was a frequently reported TEAE in patients with ADHD of all ages receiving LDX, although the available data indicated no overall worsening of sleep quality in adults. Post-marketing survey data suggest that the rate of non-medical use of LDX was lower than that for short-acting stimulants and lower than or equivalent to long-acting stimulant formulations. Small mean increases were seen in blood pressure and pulse rate in patients receiving LDX.
CONCLUSIONS
The safety and tolerability profile of LDX in individuals with ADHD is similar to that of other stimulants.
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Clinical Trials, Phase III as Topic; Dextroamphetamine; Dose-Response Relationship, Drug; Humans; Lisdexamfetamine Dimesylate; Prodrugs; Randomized Controlled Trials as Topic; Time Factors
PubMed: 24788672
DOI: 10.1007/s40263-014-0166-2 -
Psychosomatics Sep 1981
Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Blood Pressure; Child; Dextroamphetamine; Humans; Hyperkinesis; Male; Paranoid Disorders; Pulse
PubMed: 7313058
DOI: 10.1016/S0033-3182(81)73108-6 -
JAMA Jul 1975
Topics: Adolescent; Adult; Anorexia; Capsules; Child; Child, Preschool; Dextroamphetamine; Drug Evaluation; Drug Tolerance; Epilepsy; Follow-Up Studies; Humans; Hyperkinesis; Sleep Initiation and Maintenance Disorders; Time Factors
PubMed: 1173843
DOI: No ID Found -
The Journal of Clinical Psychiatry Oct 1987Five of six acutely manic patients treated with dextroamphetamine experienced a 50% or greater reduction in their mania severity scores. Side effects were noted in only... (Clinical Trial)
Clinical Trial
Five of six acutely manic patients treated with dextroamphetamine experienced a 50% or greater reduction in their mania severity scores. Side effects were noted in only one patient. The treatment results suggest that dextroamphetamine might be useful in the treatment of mania.
Topics: Acute Disease; Adult; Bipolar Disorder; Clinical Trials as Topic; Dextroamphetamine; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales
PubMed: 3312177
DOI: No ID Found -
Neuropsychopharmacology : Official... Apr 2022The poor translatability between preclinical and clinical drug trials has limited pro-cognitive therapeutic development. Future pro-cognitive drug trials should use... (Randomized Controlled Trial)
Randomized Controlled Trial
The poor translatability between preclinical and clinical drug trials has limited pro-cognitive therapeutic development. Future pro-cognitive drug trials should use translatable cross-species cognitive tasks with biomarkers (1) relevant to specific cognitive constructs, and (2) sensitive to drug treatment. Here, we used a difficulty-modulated variant of a cross-species cognitive control task with simultaneous electroencephalography (EEG) to identify neurophysiological biomarkers sensitive to the pro-cognitive effects of dextroamphetamine (d-amp) (10 or 20 mg) in healthy adults (n = 23), in a randomized, placebo-controlled, counterbalanced, double blind, within-subject study, conducted across three test days each separated by one week. D-amp boosted d-prime, sped reaction time, and increased frontal P3a amplitude to non-target correct rejections independent of task difficulty. Task difficulty did however, moderate d-amp effects on EEG during target performance. D-amp suppressed frontal theta power during easy target responses which negatively correlated with drug-induced improvement in hit rate while d-amp-induced changes in P3b amplitude during hard target trials strongly correlated with drug-induced improvement in hit rate. In summary, d-amp affected both behavioral and neurophysiological measures of cognitive control elements. Under low-demand, d-amp diminished cognitive control by suppressing theta, yet under high-demand it boosted control in concert with higher P3b amplitudes. These findings thus appear to reflect a gain-sharpening effect of d-amp: during high-demand processes were boosted while during low-demand processes were neglected. Future studies will use these neurophysiological measures of cognitive control as biomarkers to predict d-amp sensitivity in people with cognitive control deficits, including schizophrenia.
Topics: Adult; Humans; Cognition; Dextroamphetamine; Electroencephalography; Healthy Volunteers
PubMed: 35042948
DOI: 10.1038/s41386-021-01257-2 -
Paediatric Drugs 2007Lisdexamfetamine is an amphetamine prodrug, comprising an l-lysine amino acid covalently bonded to dextroamphetamine (d-amphetamine). Lisdexamfetamine is approved in the... (Review)
Review
Lisdexamfetamine is an amphetamine prodrug, comprising an l-lysine amino acid covalently bonded to dextroamphetamine (d-amphetamine). Lisdexamfetamine is approved in the US for the treatment of attention-deficit hyperactivity disorder in children aged 6-12 years. Lisdexamfetamine is a therapeutically inactive molecule. After oral ingestion, lisdexamfetamine is hydrolyzed to l-lysine, a naturally occurring essential amino acid, and active d-amphetamine, which is responsible for the activity of the drug. In a well designed pharmacodynamic study in adult stimulant abusers, 50 or 100 mg doses of oral lisdexamfetamine had less likability than d-amphetamine 40 mg, suggesting a reduced abuse potential. Through rate-limited hydrolysis in the body, l-lysine is cleaved, gradually releasing pharmacologically active d-amphetamine. The pharmacokinetics of lisdexamfetamine suggest a reduced potential for abuse. In two well designed trials in children aged 6-12 years with attention-deficit hyperactivity disorder (ADHD), the efficacy of lisdexamfetamine was superior to that of placebo in improving symptoms associated with ADHD. Adverse events with lisdexamfetamine were, in general, mild to moderate in severity and consistent with those commonly reported with amphetamine.
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Clinical Trials as Topic; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate
PubMed: 17407369
DOI: 10.2165/00148581-200709020-00007 -
Pediatrics Feb 1974
Clinical Trial Comparative Study
Topics: Aggression; Anxiety; Attention; Child; Child Behavior Disorders; Child, Preschool; Clinical Trials as Topic; Dextroamphetamine; Drug Tolerance; Evaluation Studies as Topic; Female; Humans; Hyperkinesis; Male; Methylphenidate; Placebos; Psychological Tests; Social Behavior
PubMed: 4590730
DOI: No ID Found -
The New Zealand Medical Journal Jan 1972
Topics: Amphetamine; Dextroamphetamine; Drug Industry; New Zealand
PubMed: 4502632
DOI: No ID Found