This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
This article has been cited by other articles in PMC. Abstract Amphetamine was discovered over years ago. Keywords: Abuse liability, amphetamine, attention deficit hyperactivity disorder ADHD , drug formulations, lisdexamfetamine, microdialysis.
Open in a separate window. Figure 1. Table 1. Amphetamines — past and present. IR: immediate release; XR: extended release. A clinical perspective on the use of amphetamine in the treatment of ADHD ADHD is arguably the most under-diagnosed and treated of all psychiatric disorders, especially in adults Kooij et al.
The pharmacology of amphetamine The chemical structure, particularly the 3-dimensional 3-D structure of amphetamine, is critical in determining the pharmacological effects that underpin its considerable therapeutic benefits and also its liability for recreational abuse. Figure 2. Actions comprising the pharmacological mechanism of amphetamine. Figure 3. Table 2. Figure 4. Figure 5. Clinical implications The primary action of amphetamine is to increase synaptic concentrations of monoamine neurotransmitters, thereby indirectly enhancing noradrenergic, dopaminergic neurotransmission in the CNS.
Efficacy It has long been accepted that in ADHD there is dysregulation of the brain catecholaminergic systems in the PFC and its connections to subcortical regions including the striatum Arnsten and Dudley, ; Durston, ; Russell et al. Safety and adverse events With clinical applications of amphetamine as a drug to combat fatigue, an appetite suppressant and a treatment of narcolepsy, adverse effects such as anorexia, weight loss and insomnia are predictable and frequent adverse events associated with the use of amphetamine-based medications in the management of ADHD.
Abuse liability Stimulants have a tendency to be liked by a certain proportion of the population, though not by everyone by any means. Once-daily formulations In previous reviews, we have extensively described the efficacy and safety of stimulant and non-stimulant drugs used in the management of ADHD and compared the relative merits of each Heal et al. Lisdexamfetamine As briefly discussed earlier in the review, lisdexamfetamine is the first amphetamine prodrug to have been approved for use in treating ADHD.
Table 3. Data on file Shire Pharmaceuticals, Implications of pharmacokinetics of lisdexamfetamine for efficacy, safety and recreational abuse liability The efficacy of lisdexamfetamine has been demonstrated in a number of randomised, double-blind, placebo-controlled clinical trials in ADHD in children, adolescents Biederman et al.
Table 4. LDX: lisdexamfetamine. Figure 6. Conclusions It is now just over a hundred years since amphetamine was first discovered. Footnotes Conflict of interest: The authors declare that there are no conflict of interest.
References Adderall XR U. American Psychiatric Association The diagnostic and statistical manual of mental disorders, fourth edition. Replication, time response, and differential effect by diagnostic group and family rating.
Behav Brain Funct 1 : 2. Synapse 36 : — [ PubMed ] [ Google Scholar ]. Bett WR. Bolden-Watson C, Richelson E. Bradley C. Am J Psychiat 94 : — [ Google Scholar ]. Neuropsychopharmacology 27 : — [ PubMed ] [ Google Scholar ].
Castellanos FX. New York: Oxford University Press, pp. Charnaud B, Griffiths V. Society for Neurosciences.
Abstract Available online at: www. Connell PH. Clinical manifestations and treatment of amphetamine type of dependence. Di Chiara G, Imperato A. Clinical and biochemical findings. Durston S. Neuropharmacology 52 : — [ PubMed ] [ Google Scholar ]. A [fluorine]fluorodopa positron emission tomographic study.
Faraone SV, Buitelaar J. MedGenMed 8 : 4. Gilbert D, Cooper SJ. Gross MD. A comparison of d- amphetamine and racemic-amphetamine in the treatment of the hyperkinetic syndrome or minimal brain dysfunction.
Guttmann E, Sargent W. Neuropharmacology 57 : — [ PubMed ] [ Google Scholar ]. Howland RH. Abstract number Jasinski D. Protocol No: NRP Jasinski DR. Jasinski DR, Krishnan S. Open label, single-centre, Phase I study in healthy adult volunteers. Neuropharmacology 30 : 89—92 [ PubMed ] [ Google Scholar ]. Madaan V. Mattingly G. Miller L, Griffith J. Psychopharmacology 80 : — [ PubMed ] [ Google Scholar ]. Najib J. Neuropsychopharmacology 2 : — [ PubMed ] [ Google Scholar ].
Synapse 6 : — [ PubMed ] [ Google Scholar ]. Transdermal methylphenidate, behavioral, and combined treatment for children with ADHD. Pediatrics : — [ PubMed ] [ Google Scholar ]. Pediatrics 86 : — [ PubMed ] [ Google Scholar ]. In one trial, Tolerability : The most commonly observed adverse effects in clinical trials, with an incidence at least twice that of placebo, are dyspepsia, nausea, vomiting, fatigue, decreased appetite, and mood swings.
Effectiveness : Atomoxetine is more effective than placebo for the treatment of ADHD in children and adults. In four randomized, double-blind, placebo-controlled trials of nine weeks or less, atomoxetine was statistically more effective than placebo in reducing the ADHD Rating Scale scores in children ages six to 18 years.
A week single open-label trial of patients randomized in a ratio to atomoxetine or methylphenidate found no difference in patient outcomes, but the trial was limited by the small number of patients receiving methylphenidate; the failure to conceal allocation to groups; short follow-up; and the lack of blinding of patients, physicians, and those who assessed outcomes.
Twice-daily dosing will double the cost. Average wholesale costs are based on Red Book, Montvale, N. Simplicity : Atomoxetine is not a controlled substance, and it does not require observance of the stringent prescribing rules necessary for Schedule II drugs, such as methyl-phenidate and dextroamphetamine.
Dosing of atomoxetine, unfortunately, is not straightforward because of the potential for excessive dosing in patients who are slow metabolizers. Children should be started at a low dose of 0. If tolerated, the dose can be increased after at least three days to a target daily dose of 1. This may be given once a day or in divided doses, and it must be approximated using capsules.
No liquid formulation is available. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. For Immediate Release: May 30, Related Information. Sci Pharmtech [Taiwan]. US Patent 8,,, Oct. View the full-text patent here. You are commenting using your WordPress. You are commenting using your Google account. You are commenting using your Twitter account.
You are commenting using your Facebook account. Notify me of new comments via email. Notify me of new posts via email. This site uses Akismet to reduce spam.
Learn how your comment data is processed. Radhakrishnan and Dr B. His friends call him Open superstar worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 30 PLUS year tenure till date June , Around 35 plus products in his career.
He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc. Blog at WordPress. Search Search. New Drug Approvals. Blog Stats 3,, hits. Follow Blog via Email Enter your email address to follow this blog and receive notifications of new posts by email. Join 2, other followers. Top Clicks patentimages. Atomoxetine is the first non-stimulant drug approved for the treatment of attention-deficit hyperactivity disorder ADHD.
0コメント