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    Dexmethylphenidate molecular structure

    Dexmethylphenidate Stats & Data

    Focalin xr Dextromethylphenidate Dexmethylphenidate er Dexmethylphenidate hcl er Dexmethylphenidate extended-release focalin
    NPS DataHub
    MW233.31
    FormulaC14H19NO2
    CAS40431-64-9
    IUPACmethyl (2R)-2-phenyl-2-[(2R)-piperidin-2-yl]acetate
    SMILESCOC(=O)C(C1CCCCN1)c1ccccc1
    InChIKeyDUGOZIWVEXMGBE-CHWSQXEVSA-N
    Phenethylamines; 2020/1. Von 2-Phenethylamin abgeleitete Verbindungen; 2021/1. Von 2-Phenethylamin abgeleitete Verbindungen; 2022/1. Von 2-Phenethylamin abgeleitete Verbindungen
    Psychoactive Class Stimulant

    Pharmacology

    DrugBank
    State Solid Vd 2.65L/kg when administered intravenously.

    Description

    Dexmethylphenidate is the dextrorotary form of methylphenidate introduced in 2002. It is a norepinephrine-dopamine reuptake inhibitor (NDRI) and thus a psychostimulant. It is used for treatment of Attention Deficit Hyperactivity Disorder (ADHD). The d-isomer is thought to have greater effect with fewer side effects than the l-isomer or the racemic mixture.

    Mechanism of Action

    Methylphenidate inhibits dopamine and norepinephrine reuptake transporters in synapses, especially in the thalamus and striatum. One study shows no detectable difference in the caudal prefrontal cortex of treated or untreated monkeys, though multiple rat studies show activity on the prefrontal cortex. Imaging of human brains after administration of methylphenidate shows changes to blood flow of various regions of the brain including the striatum, supplementary motor area, and posterior parietal cortex.

    Pharmacodynamics

    Dexmethylphenidate is the d-enantiomer of methylphenidate. This enantiomer is more pharmacologically active than the racemic mixture and may block norepinephrine and dopamine reuptake in synapses.

    Metabolism

    Dexmethylphenidate is metabolised to the inactive metabolite ritalinic acid by carboxylesterase 1A1 in the liver. Other minor pathways metabolise dexmethylphenidate to the inactive metabolites 6-oxo-methylphenidate and p-hydroxy-methylphenidate which are de-esterified and conjugated into other unknown metabolites.

    Absorption

    Taking dexmethylphenidate with or without food does not affect patients in a clinically relevant way. 90% of an oral dose is absorbed but as a result of hepatic first pass metabolism, oral bioavailability of dexmethylphenidate is 23% compared to l-methylphenidate with an oral bioavailability of 5% . Maximum concentration is generally reached in 1-1.5 hours.

    Toxicity

    There is no difference in effect across genders. The difference in effect across racial groups, patients under 6 years, renal impairment, hepatic impairment, pregnancy, lactation, and geriatric patients has not been well studied. Patients with renal impairment are not expected to need dose adjustment as the drug is not mainly cleared renally. Animal studies in pregnant and lactating rats showed delayed fetal skeletal ossification, and reduced weight gain in male offspring. Due to these studies, caution must be exercised and the benefits and risks of taking this drug must be weighed. It is unlikely that dexmethylphenidate is carcinogenic but B6C3F1 mice, which are sensitive to the development of hepatic tumours, developed hepatoblastomas at 2 times the maximum recommended human dose. Methylpheidate was not found to be mutagenic but is weakly clastogenic in Chinese Hamster Ovary cells. Methylphenidate does not impair fertility in animal studies.

    Indication

    Dexmethylphenidate is used as a treatment for ADHD, ideally in conjunction with psychological, educational, behavioral or other forms of treatment.

    Half-life

    The mean terminal half life is approximately 2.2 hours. However other studies have shown 3.8-3.9 hours, or 5.96 hours after intravenous administration and 5.69 hours following an oral dose.

    Protein Binding

    12-15% of dexmethylphenidate is protein bound. However, other studies have observed 15.2±5.2% protein binding in children and 16.2±1.1% in adults.

    Elimination

    Dexmethylphenidate is mainly eliminated renally. After 48 hours, 90% of the dose is collected in the urine and 3.3% is collected from feces.

    Clearance

    0.40L/hr/kg following an intravenous dose and a renal clearance of 0.005L/hr/kg.

    History & Culture

    Dexmethylphenidate is the dextrorotatory enantiomer of methylphenidate, isolated and developed as a separate pharmaceutical product. It received approval for medical use in the United States in 2001 and was subsequently introduced to the market in 2002 under the brand name Focalin. The rationale for its development was that the d-isomer was believed to be the more pharmacologically active component of the racemic methylphenidate mixture. Since its introduction, dexmethylphenidate has become widely prescribed for the treatment of attention deficit hyperactivity disorder. Generic formulations have become available, expanding access beyond the original brand-name product. By 2023, it had become the 127th most commonly prescribed medication in the United States, with more than 4 million prescriptions written annually.

    Effect Profile

    Curated + 15 Reports
    Stimulant 4.2

    Strong euphoria with moderate anxiety/jitters, mild stimulation

    Stimulation / Energy×3
    4
    Euphoria / Mood Lift×2
    9
    Focus / Productivity×2
    0
    Anxiety / Jitters×1
    6

    Tolerance & Pharmacokinetics

    drugs.wiki

    Tolerance Decay

    Full tolerance 1d Half tolerance 12d Baseline ~21d

    Cross-Tolerances

    Amphetamine
    30% ●○○
    Methamphetamine
    30% ●○○
    Lisdexamfetamine
    30% ●○○
    2-FA
    30% ●○○
    2-FMA
    30% ●○○
    3-FA
    30% ●○○
    4-FA
    30% ●○○
    4-FMA
    30% ●○○

    Experience Report Analysis

    Erowid
    15 Reports
    2004–2015 Date Range
    7 With Age Data
    14 Effects Detected

    Demographics

    Gender Distribution

    Age Distribution

    Reports Over Time

    Effect Analysis

    Erowid

    Effects aggregated from 15 experience reports (15 Erowid)

    15 Reports
    14 Effects Detected
    6 Positive
    5 Adverse
    3 Neutral

    Effect Sentiment Distribution

    Confidence Distribution

    Positive Effects 6

    Euphoria 66.7% 70%
    Stimulation 53.3% 70%
    Focus Enhancement 46.7% 70%
    Empathy 33.3% 70%
    Music Enhancement 26.7% 70%
    Tactile Enhancement 26.7% 70%

    Adverse Effects 5

    Anxiety 33.3% 70%
    Increased Heart Rate 26.7% 70%
    Sweating 20.0% 70%
    Pupil Dilation 20.0% 70%
    Memory Suppression 20.0% 70%

    Real-World Dose Distribution

    62K Doses

    From 30 individual dose entries

    Insufflated (n=14)

    Median: 10.0mg 25th: 10.0mg 75th: 27.5mg 90th: 30.0mg
    mg/kg median: 0.158 mg/kg 75th: 0.452

    Oral (n=16)

    Median: 10.0mg 25th: 5.0mg 75th: 20.0mg 90th: 25.0mg
    mg/kg median: 0.184 mg/kg 75th: 0.353

    Form / Preparation

    Most common forms and preparations reported

    Body-Weight Dosing

    Dose relative to body weight from reports with weight data

    Median: 0.163 mg/kg IQR: 0.143–0.259 mg/kg n=7

    Redose Patterns

    Redosing behavior across 11 reports

    54.5% Redosed
    2.2 Avg Doses
    75m Median Interval

    Legal Status

    Country Status Notes
    United States Prescription medication Marketed as a prescription product under the brand name Focalin since November 2001. Generic formulations (Dexmethylphenidate HCl) are also available from multiple pharmaceutical manufacturers including Sandoz and Adare Pharmaceuticals.
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