The metabolic fate of amphetamine in man and other species

Dring, L. G.; Smith, Robert L.; Williams, R. T.

doi:10.1042/bj1160425

Cited by 247 publications

(63 citation statements)

References 29 publications

(14 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In mammals, amphetamine is metabolized along two major pathways which are differentially employed by various species [47]. In the first pathway, hydroxylation of amphetamine via CYP2D6 yields p-hydroxy-amphetamine.…”

Section: Metabolic Pathways and Pharmacokineticsmentioning

confidence: 99%

The Pharmacogenomic Era: Promise for Personalizing Attention Deficit Hyperactivity Disorder Therapy

Stein

McGough²

2008

Child and Adolescent Psychiatric Clinics of North America

View full text Add to dashboard Cite

SynopsisCurrently, ADHD treatment is often determined empirically through trial and error until an adequate response is obtained or side effects occur. ADHD is highly heritable and there is wide individual variability in response to ADHD medications, suggesting that the mechanism of action of stimulant medications may provide clues for genetic predictors of response. The promise of ADHD pharmacogenetics is far reaching, and includes the potential to develop individualized medication regimens that improve symptom response, decrease risk for side effects, improve long-term tolerability, and thus contribute to long-term treatment compliance and improved general effectiveness. Early ADHD pharmacogenetic studies have focused predominantly on catecholamine pathway genes and response to methylphenidate. Future efforts will also examine a wider range of stimulant and non-stimulant medications on a range of outcome measures and time periods. Based upon these studies, the potential for personalizing ADHD treatment in clinical practice will be determined. IntroductionAttention-Deficit/Hyperactivity Disorder (ADHD) is a common and treatable behavioral syndrome that typically emerges during childhood or adolescence and often persists into adulthood. There are an increasing number of stimulant and non-stimulant medication options for ADHD, with numerous new compounds in development [1]. In acute treatment studies, stimulant medications generally demonstrate large effect sizes on ADHD symptom reduction relative to placebo, with slightly smaller effect sizes in adult studies [2]. Surprisingly, only a minority of children and adolescents with ADHD remain on medication consistently Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. despite persistence of symptoms and impairments. Even among responders, there is marked variability in optimal dosage, duration of effect, and tolerability. Moreover, in spite of acute symptom reduction from ADHD medications, as yet there is little evidence of long-term response and improvement in functioning among those children who received treatment [4,5]. Furthermore, there are few reliable predictors of medication response. In the absence of these data, treatment is often determined "empirically" in clinical practice through a gradual titration of different dosages and trial and error approach to different medications. NIH Public AccessADHD is a highly heritable disorder [6]. The search for candidate genes associated with ADHD has been largely driven by the understanding that medications for the disorder have drug targets in the catecholamine system [7]. Conve...

show abstract

Section: Metabolic Pathways and Pharmacokineticsmentioning

confidence: 99%

The Pharmacogenomic Era: Promise for Personalizing Attention Deficit Hyperactivity Disorder Therapy

Stein

McGough²

2008

Child and Adolescent Psychiatric Clinics of North America

View full text Add to dashboard Cite

show abstract

“…1A). 1) While a portion of the MP ingested is N-demethylated to AP, the other pathways of MP metabolism are similar to those of AP. 2,4) For example, MP is also converted to p-hydroxylated metabolites and benzoic acid (Fig.…”

Section: Amphetamines Including Mdmamentioning

confidence: 99%

“…[1][2][3][4] Although unchanged AP and MP are easily detectable in urine of abusers, a large fraction of these drugs is metabolized in the body following absorption. The major metabolites of AP in man are p-hydroxy-AP and benzoic acid including its glycine conjugate (Fig.…”

Section: Amphetamines Including Mdmamentioning

confidence: 99%

Metabolism of Drugs of Abuse: Its Contribution to the Toxicity and the Inter-Individual Differences in Drug Sensitivity

Yamada

Ishii

Oguri

2005

JOURNAL OF HEALTH SCIENCE

View full text Add to dashboard Cite

Abuse of drugs remains a serious and world-wide problem. As exemplified by opioids, there are large interindividual differences in the effects and toxicity of drugs. However, the mechanism underlying such inter-individual differences remains largely unknown. Since, in many cases, drug metabolism affects the effects of drugs, the different metabolic capacity of individuals may explain these inter-individual differences. In this review, we shall focus on drugs of abuse and survey briefly their metabolism and the enzymes involved. In addition, we shall discuss the putative origin of the inter-individual differences in sensitivity to drugs of abuse.

show abstract

“…The calibration ranges for AP and RA were established in order to cover the majority of the real urine sample concentrations based on previous studies. 8,20,22 The calibration curves for the analytes were linear in the range of the tested concentrations with the coefficient of determination (r 2 ≥ 0.9952). All the linearity coefficients of the calibration curves were higher than the accepted criterion (r 2 > 0.99), indicating an acceptable linear relationship.…”

Section: Evaluation Of the Validation Datamentioning

confidence: 99%

“…[3][4][5] MPH is extensively metabolized in the human liver and its main urinary metabolite is ritalinic acid (RA), as the deesterified product, 6,7 while AP is metabolized to benzoic acid, 1-phenylpropan-2-one and 4-hydroxyamphetamine (HAP), of which the active sympathomimetic amine is HAP. 8 Recently, the incidence of ADHD diagnosis has significantly increased, along with the use of prescription psychostimulants. 9,10 In addition, the illicit use of prescription ADHD medications has gained increasing interest among students in Republic of Korea and other countries.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Determination of Methylphenidate, Amphetamine and their Metabolites in Urine using Direct Injection Liquid Chromatography-Tandem Mass Spectrometry

Kwon¹,

Suh²,

In³

et al. 2014

Mass Spectrometry Letters

View full text Add to dashboard Cite

Nonmedical use of prescription stimulants such as methylphenidate (MPH) and amphetamine (AP) by normal persons has been increased to improve cognitive functions. Due to high potential for their abuse, reliable analytical methods were required to detect these prescription stimulants in biological samples. A direct injection liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and implemented for simultaneous determination of MPH, AP and their metabolites ritalinic acid (RA) and 4-hydroxyamphetamine (HAP) in human urine. Urine sample was centrifuged and the upper layer (100 µL) was mixed with 800 µL of distilled water and 100 µL of internal standards (0.2 µg/mL in methanol). The mixture was then directly injected into the LC-MS/MS system. The mobile phase was composed of 0.2% formic acid in distilled water (A) and acetonitrile (B). Chromatographic separation was performed by using a Capcell Pak MG-II C18 (150 mm × 2.0 mm i.d., 5 µm, Shiseido) column and all analytes were eluted within 5 min. Linear least-squares regression with a 1/x weighting factor was used to generate a calibration curve and the assay was linear from 20 to 1500 ng/mL (HAP), 40-3000 ng/mL (AP and RA) and 2-150 ng/mL (MPH). The intra-and inter-day precisions were within 16.4%. The intra-and inter-day accuracies ranged from -15.6% to 10.8%. The limits of detection for all the analytes were less than 4.7 ng/mL. The suitability of the method was examined by analyzing urine samples from drug abusers.

show abstract

The metabolic fate of amphetamine in man and other species

Cited by 247 publications

References 29 publications

The Pharmacogenomic Era: Promise for Personalizing Attention Deficit Hyperactivity Disorder Therapy

The Pharmacogenomic Era: Promise for Personalizing Attention Deficit Hyperactivity Disorder Therapy

Metabolism of Drugs of Abuse: Its Contribution to the Toxicity and the Inter-Individual Differences in Drug Sensitivity

Simultaneous Determination of Methylphenidate, Amphetamine and their Metabolites in Urine using Direct Injection Liquid Chromatography-Tandem Mass Spectrometry

Contact Info

Product

Resources

About