Pharmacology of methylphenidate, amphetamine enantiomers and pemoline in attention-deficit hyperactivity disorder

Patrick, Kennerly S.; Markowitz, John S.

doi:10.1002/(sici)1099-1077(199711/12)12:6<527::aid-hup932>3.0.co;2-u

Cited by 119 publications

(74 citation statements)

References 142 publications

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“…Clinical experience has demonstrated that at least 30% of patients are either nonresponders or are intolerant to a major psychostimulant medication (methylphenidate or amphetamine) (Greenhill et al, 1999;Patrick and Markowitz, 1998). Additionally, up to 70% of children and adolescents with ADHD also have a comorbid disorder such as conduct disorder, or anxiety (Spencer et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Interactions of attention-deficit/hyperactivity disorder therapeutic agents with the efflux transporter P-glycoprotein

Zhu

Wang

Donovan

et al. 2008

European Journal of Pharmacology

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The objective of this study was to assess the potential interactions of the drug transporter Pglycoprotein with attention-deficit/hyperactivity disorder (ADHD) therapeutic agents atomoxetine -and the individual isomers of methylphenidate, amphetamine, and modafinil utilizing established in vitro assay. An initial ATPase assay indicated that both d-and l-methylphenidate have weak affinity for P-glycoprotein. The intracellular accumulation of P-glycoprotein substrates doxorubicin and rhodamine123 in the P-glycoprotein overexpressing cell line LLC-PK1/MDR1 was determined to evaluate potential inhibitory effects on P-glycoprotein. The results demonstrated that all compounds, except both modafinil isomers, significantly increased doxorubicin and rhodamine123 accumulation in LLC-PK1/MDR1 cells at higher concentrations. To investigate the P-glycoprotein substrate properties, the intracellular concentrations of the tested compounds in LLC-PK1/MDR1 and P-glycoprotein negative LLC-PK1 cells were measured in the presence and absence of the Pglycoprotein inhibitor PSC833. The results indicate that the accumulation of d-methylphenidate in LLC-PK1 cells was 32.0% higher than in LLC-PK1/MDR1 cells. Additionally, coadministration of PSC833 leads to 52.9% and 45.6% increases in d-modafinil and l-modafinil accumulation, respectively, in LLC-PK1/MDR1 cells. Further studies demonstrated that l-modafinil transport across LLC-PK1/MDR1 cell monolayers in the basolateral-to-apical (B-A) direction was significantly higher than in the apical-to-basolateral (A-B) direction. PSC833 treatment significantly decreased the transport of l-modafinil in B-A direction. In conclusion, our results suggest that all tested agents with the exception of modafinil isomers are relatively weak P-glycoprotein inhibitors. Furthermore, P-glycoprotein may play a minor role in the transport of d-methylphenidate, dmodafinil, and l-modafinil.

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Section: Discussionmentioning

confidence: 99%

Interactions of attention-deficit/hyperactivity disorder therapeutic agents with the efflux transporter P-glycoprotein

Zhu

Wang

Donovan

et al. 2008

European Journal of Pharmacology

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“…Attention deficit hyperactivity disorder (ADHD) is a developmental disorder that affects as much as 5 -15% of school-aged children in the United States [4,27]. MPD is a stimulant of the central nervous system (CNS) with a neuropharmacological profile similar to psychostimulants such as amphetamine and cocaine [29,42]. Cocaine, amphetamine, and MPD are known as indirect dopamine agonists [11,24,42,61].…”

Section: Introductionmentioning

confidence: 99%

“…MPD is a stimulant of the central nervous system (CNS) with a neuropharmacological profile similar to psychostimulants such as amphetamine and cocaine [29,42]. Cocaine, amphetamine, and MPD are known as indirect dopamine agonists [11,24,42,61]. There are anectodal reports that catecholerminergic agonists affect adolescent rats differently as compared to adult rats [5,31,57,63].…”

Section: Introductionmentioning

confidence: 99%

Acute and chronic methylphenidate dose–response assessment on three adolescent male rat strains

Peng¹,

Swann²,

Dafny³

2006

Brain Research Bulletin

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Methylphenidate (MPD), commonly known as Ritalin, is the most frequently prescribed drug to treat children and adults with attention deficit hyperactivity disorder (ADHD). Adolescence is a period of development involving numerous neuroplasticities throughout the central nervous system (CNS). Exposure to a psychostimulant such as MPD during this crucial period of neurodevelopment may cause transient or permanent changes in the CNS. Genetic variability may also influence these differences. Thus, the objective of the present study was to determine whether acute and chronic administration of MPD (0.6, 2.5, or 10.0 mg/kg, i.p.) elicit effects among adolescent WKY, SHR, and SD rats and to compare whether there were strain differences. An automated, computerized, open-field activity monitoring system was used to study the dose response characteristics of acute and repeated MPD administration throughout the 11-day experimental protocol. Results showed that all three adolescent rat groups exhibited dose-response characteristics following acute and chronic MPD administration, as well as strain differences. These strain differences depended on the MPD dose and locomotor index. Chronic treatment of MPD in these animals did not elicit behavioral sensitization, a phenomenon described in adult rats that is characterized by the progressive augmentation of the locomotor response to repeated administration of the drug. These results suggest that the animal's age at time of drug treatment and strain/genetic variability play a crucial role in the acute and chronic effect of MPD and in the development of behavioral sensitization.

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“…Additionally, alcohol has been shown to be associated with the leading causes of death in young adults [10], and alcohol dependence predisposes individuals to becoming dependent on non-medical stimulants [11]. Subjects who have co-administered MPD and ethanol have reported decreased feelings of the alcohol's effects as compared to when ethanol is consumed individually [40], resulting in increased ethanol consumption compared to when ethanol is taken alone [32]. Additionally, adolescent spontaneously hyperactive rats (SHR) the animal model for ADHD, when chronically treated with MPD have shown increased alcohol drinking upon the adult stage [41].…”

Section: Response Characteristics Of Ethanol Alone and After Chronic mentioning

confidence: 99%

Ritalin Use Modifies Alcohol Effects in Rats

Sonne¹,

Dafny²

2014

JBBS

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Methylphenidate (MPD), known as Ritalin, is a common drug prescribed for those diagnosed with Attention Deficit Hyperactivity Disorder (ADHD).There are reports that many MPD users consume alcohol, resulting in toxic effects and hospitalization. The goal of this study was to investigate the effects of ethanol in rats concomitant with acute and repetitive MPD exposure. Rats were divided into four groups, control (saline), 0.6 mg/kg MPD, 2.5 mg/kg MPD, and 10.0 mg/kg MPD groups and lasted for 12 consecutive days. Ethanol was given after repeated MPD administration as follows. On experimental day 1 (ED 1), all animals were treated with saline to establish baseline, on ED 2 through ED 7 either saline or MPD (0.6, 2.5, or 10.0 mg/kg) was given. On ED 11, after three days without treatment (ED 8 -10), rats were treated as they were on ED 2 -7. At ED 12, 1 g/kg ethanol was administered, and one hour of locomotor activity was recorded after alcohol administration, using the open field assay. The data show a dose response characteristic of increased locomotor activity with increasing doses of MPD. Ethanol administration alone depresses locomotor activity. The depressive effect of alcohol was significantly attenuated in animals treated with MPD, in a dose dependent manner. The higher dose of MPD previously administered resulted in a larger attenuation of the ethanol's suppressive effect. These trends demonstrate that chronic MPD exposure directly influences the effects of alcohol in rats. Under these circumstances, it is reasonable to assume that a subject will need to consume an increased amount of ethanol in order to attain the ethanol effect desired. This discrepancy between effects and exposure may be a liability for ethanol toxicity.

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Pharmacology of methylphenidate, amphetamine enantiomers and pemoline in attention-deficit hyperactivity disorder

Cited by 119 publications

References 142 publications

Interactions of attention-deficit/hyperactivity disorder therapeutic agents with the efflux transporter P-glycoprotein

Interactions of attention-deficit/hyperactivity disorder therapeutic agents with the efflux transporter P-glycoprotein

Acute and chronic methylphenidate dose–response assessment on three adolescent male rat strains

Ritalin Use Modifies Alcohol Effects in Rats

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