Drug Database
ME

methylphenidate (Methydur)

✓ Approved

Durect · SLC6A2 · Small Molecule

What is methylphenidate?

methylphenidate is a small molecule developed by Durect. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesMethydur
CompanyDurect
Drug ClassSmall Molecule
Molecular TargetSLC6A2, SLC6A3
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Durect

Mechanism of Action

Molecular Targets

methylphenidate acts on 2 molecular targets:

SLC6A2solute carrier family 6 member 2 (NAT1, NET)
SLC6A3solute carrier family 6 member 3 (PKDYS, DAT1)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

methylphenidate is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Psychiatric disordersAttention deficit hyperactivity disorder✓ Approved

Related Research Articles

PubMedMovement disorders clinical practice2026-10-22

When Tics and Autism Meet: Phenomenology, Severity, and Treatment Patterns.

Aldurayhim Fatimah F, Martino Davide D, Sarna Justyna R JR, Pringsheim Tamara T

Tic disorders frequently co-occur with neurodevelopmental conditions, including autism spectrum disorder (ASD). However, the impact of ASD on tic phenomenology, severity, and treatment patterns remains incompletely understood. To compare clinical characteristics, tic phenomenology, severity, and treatment patterns in individuals with tic disorders with and without comorbid ASD. We conducted a cross-sectional analysis of 535 participants from Calgary Child and Adult Tic Disorders Clinical Registries. Tic severity was assessed using the Yale Global Tic Severity Scale (YGTSS). Comorbidities, tic phenomenology, and pharmacological treatments were recorded. ASD and non-ASD groups were compared using t-tests and chi-square tests. Mean age at tic onset was 6.79 years; 73.3% were male, and 9.2% had ASD. ASD was associated with higher rates of complex motor (arm 20.4% vs 9.9%; hand 24.5% vs 13.9%) and vocal tics (phrases 12.2% vs 3.5%; palilalia 20.4% vs 8.3%; blocking/stuttering 16.3% vs 6.2%) compared with non-ASD participants (all P < 0.05), with similar overall severity. ASD was also associated with higher rates of ADHD (81.6% vs 44.7%) and greater use of guanfacine, aripiprazole, risperidone, methylphenidate, and dextroamphetamine compared with non-ASD participants (all P < 0.05). In multivariable analysis, ASD was independently associated with lower tic-related impairment (β = -4.49, 95% CI -8.46 to -0.51; P = 0.027). Comorbid ASD in tic disorders is associated with higher rates of complex motor and vocal tics, while severity is similar to non-ASD. Lower tic-related impairment may reflect communication differences. Comorbid symptoms influenced treatment supporting the need for individualized management.

PMID 42902960
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PubMedBMC gastroenterology2026-10-20

Parabacteroides distasonis ameliorates methylphenidate hydrochloride-induced colonic inflammatory responses and associated gastrointestinal distress.

Yao Jinwen J, Gao Xia X, Zhu Lin L, Wang Linlin L et al.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in childhood, with methylphenidate hydrochloride (MPH) as its first-line pharmacotherapy. Though effective, MPH is associated with underrecognized gastrointestinal adverse events warranting further investigation. Recently, the gut microbiota has attracted attention for treating gastrointestinal distress, but research on its role in alleviating MPH-induced gastrointestinal reactions remains scarce. Herein, Wistar-Kyoto rats (WKY) served as controls alongside spontaneously hypertensive rats (SHR) to explore MPH-induced gastrointestinal adverse drug reactions. The gastrointestinal phenotypes, colonic histopathological characteristics, and inflammatory factor levels were evaluated, and the gut microbiota profiles were analyzed via 16S rRNA gene sequencing. The protective effect of Parabacteroides distasonis (P. distasonis) was further verified by supplementing the treated rats with this strain. We demonstrated MPH induced diarrhea and colonic inflammatory responses in rats. 16S rRNA gene amplicon sequencing revealed that MPH-treated rats had significantly decreased gut microbiota health index, increased dysbiosis index, and reduced P. distasonis abundance, suggesting MPH-induced gastrointestinal reactions may correlate closely with reduced P. distasonis. Further experiments confirmed that P. distasonis supplementation effectively alleviated diarrhea and colonic inflammatory responses in MPH-treated rats. Collectively, this is the first study verifying that P. distasonis supplementation mitigates MPH-induced gastrointestinal adverse reactions, providing a novel intervention strategy to improve tolerance of ADHD pharmacotherapy.

PMID 42897488
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PubMedBrain and behavior2026-10-19

Efficacy of Saffron as an Adjunct to Methylphenidate in Treating ADHD in Children Aged 6-12: A Randomized Clinical Trial.

Hosseinpourfardi Asieh A, Sahaf Seyyed Mohammad Saeid SMS, Afzaljavan Fahimeh F, Soltanifar Atefeh A et al.

Attention-deficit/hyperactivity disorder (ADHD) is a common childhood disorder often managed with stimulant medications such as methylphenidate. Around 30% of patients with ADHD do not respond to treatment or cannot tolerate its side effects, which necessitates the consideration of alternative options. This study evaluated the effectiveness of adding the saffron extract to methylphenidate on ADHD symptoms and working memory in children aged 6-12. In a randomized clinical trial, 58 children diagnosed with ADHD were randomized into two groups: a methylphenidate (0.5-1 mg/kg/day, divided into 2-3 doses)/saffron (20-30 mg/day based on weight: 20 mg for <30 kg, 30 mg for >30 kg) group and a control group receiving only methylphenidate (0.5-1 mg/kg/day, divided into 2-3 doses) for six weeks. The severity of ADHD was evaluated using subjective (Conners' Parent Rating Scale-revised) and objective (Corsi block-span task and continuous performance test) tests at the start and end (in the sixth week) of the study. 22 participants in the methylphenidate/saffron group and 21 in the control group completed the study. The changing trend of total ADHD scores (p = 0.002, Cohen's d = 0.85), hyperactivity score (p = 0.024, d = 0.62), impulsivity score (p = 0.031, d = 0.58), and attention score (p = 0.001, d = 0.92) was significantly different between groups based on subjective parent reports. However, no significant differences were found in impulsivity, inattention, or sustained attention on the CPT, though reaction time improved significantly (p = 0.023, d = 0.45). Scores on the Corsi Block Span Task indicated no significant changes in working memory between groups. The combination treatment was well-tolerated, with no reports of severe adverse effects. The findings suggest that the combination of saffron with methylphenidate may enhance subjective reports of ADHD symptoms, particularly hyperactivity and impulsivity; however, objective cognitive measures showed limited changes. Given the favorable safety profile of saffron and study limitations, this supports its potential role as a complementary option, pending confirmation in placebo-controlled trials with larger samples and long-term evaluations.

PMID 42895808
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PubMedToxicological sciences : an official journal of the Society of Toxicology2026-10-19

Paternal methylphenidate exposure alters sperm miRNAs and induces intergenerational behavioral and transcriptional changes that are largely reversed by washout.

Akaike Kanata K, Kaizaki-Mitsumoto Asuka A, Numazawa Satoshi S

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity. Methylphenidate (MPH), a first-line medication, is often used long-term and not routinely discontinued in individuals planning to have children. Guided by the Paternal Origins of Health and Disease framework, in this study, we investigated intergenerational effects of paternal MPH exposure and reversibility of sperm epigenetic changes. Male BALB/c mice received MPH (15 mg/kg) or vehicle for 28 days and were mated with untreated females immediately after treatment (F0-T1) or after a 40-day washout period (F0-T2). Behavioral tests and brain gene expression analyses were conducted in the offspring (F1), and sperm small noncoding RNA (sncRNA) profiles were examined in F0 males. Male offspring in the F0-T1-MPH group showed increased open-arm entry into the elevated plus maze and reduced expression of Maoa, Maob, and Bdnf in the medial prefrontal cortex. These changes were absent in the offspring derived from the F0-T2-MPH group. Sperm sncRNA sequencing identified 5,684 differentially expressed fragments in F0-T1-MPH mice, including marked alterations in miRNA-derived fragments, such as miR-34c-5p and miR-30e-5p. The target genes of these altered miRNAs were enriched in ADHD-related pathways, including axon guidance and Rap1 signaling. After washout, the number of differentially expressed sncRNA fragments decreased to 665, whereas the number of altered miRNA-derived fragments decreased from 383 to 7. These findings suggest that paternal MPH exposure may influence offspring behavior and brain gene expression through sperm miRNA alterations and that these effects are largely reversible following drug withdrawal.

PMID 42895295
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PubMedHuman psychopharmacology2026-10-16

Serum Tau and α-Synuclein in Children With Attention-Deficit/Hyperactivity Disorder: Cross-Sectional Associations With Methylphenidate Treatment.

Doğan Deniz D, İşeri Elvan E, Kahve Aybeniz Civan AC, Demirci Samet Can SC et al.

To compare serum total tau and α-synuclein among controls, drug-naïve children with attention-deficit/hyperactivity disorder (ADHD) and children with ADHD receiving methylphenidate. Original ELISA spreadsheets provided 26 controls, 29 evaluable drug-naïve participants and 32 methylphenidate-treated participants. Boundary-coded results (> 500 pg/mL for tau; < 938 pg/mL for α-synuclein) were assigned the recorded boundary for rank-based analyses. Groups were compared using Kruskal-Wallis tests and Dunn-Bonferroni contrasts; within-group associations used Spearman correlations. α-Synuclein differed among groups (H = 49.859, p < 0.001, ε2 = 0.570), with all pairwise contrasts significant. Tau also differed (H = 10.492, p = 0.005, ε2 = 0.101); drug-naïve ADHD had lower tau than controls, whereas the treated group differed from neither comparator after correction. The α-synuclein-tau correlation remained significant after false-discovery-rate adjustment only in drug-naïve ADHD (ρ = 0.443, adjusted p = 0.048). Serum α-synuclein and total tau showed distinct cross-sectional group patterns. These associations do not establish methylphenidate effects and require prospective confirmation.

PMID 42885479
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PubMedAmerican journal of obstetrics & gynecology MFM2026-10-16

Pregnancy and Offspring Outcomes After Prenatal Stimulant or Atomoxetine Exposure: A Systematic Review and Meta-analysis.

Komargodski Rinat R, Tillawe Abeer A, Berlin Maya M, Matok Ilan I

To evaluate associations of prenatal exposure to stimulants and atomoxetine for attention-deficit/hyperactivity disorder with pregnancy, congenital, perinatal, and neurodevelopmental outcomes. PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to March 2026. Protocol was registered in the International Prospective Register of Systematic Reviews (CRD42024506319). Randomized trials and observational studies comparing pregnancies or offspring exposed to stimulant medications, methylphenidate- or amphetamine-based agents, or atomoxetine with unexposed comparators and reported outcomes were eligible. Reporting guidance for systematic reviews and observational meta-analyses was followed. Two reviewers screened studies, extracted data, and assessed quality with the Newcastle-Ottawa Scale. Random-effects meta-analyses pooled unadjusted and adjusted estimates separately. For neurodevelopmental outcomes, comparators restricted to attention-deficit/hyperactivity disorder populations were prioritized when available. Twenty-five studies were included; 23 contributed to quantitative analyses. Exposure windows included periconceptional, first-trimester, early-, late-, or continued-pregnancy exposure. Exposure was associated with major congenital malformations in unadjusted analyses (risk ratio, 1.25; 95% confidence interval, 1.14-1.37), but not after adjustment (adjusted risk ratio, 1.04; 95% confidence interval, 0.97-1.12). No adjusted association was observed with cardiovascular malformations (adjusted risk ratio, 1.20; 95% confidence interval, 0.88-1.63), although methylphenidate showed a modest increase (adjusted risk ratio, 1.33; 95% confidence interval, 1.01-1.74). In adjusted analyses, exposure was not associated with miscarriage, preterm birth, low birth weight, small for gestational age, neonatal intensive care unit admission, neurodevelopmental disorders, autism spectrum disorder, or offspring attention-deficit/hyperactivity disorder. Low 5-minute Apgar score remained associated with exposure after adjustment (adjusted risk ratio, 1.21; 95% confidence interval, 1.03-1.42). Lower adjusted autism spectrum disorder risk with stimulants was not replicated in methylphenidate-specific analyses. Prenatal exposure to stimulants or atomoxetine for attention-deficit/hyperactivity disorder was not associated with increased adjusted risk of major congenital malformations or most adverse pregnancy, perinatal, and neurodevelopmental outcomes. Attenuation of crude associations after adjustment suggests confounding by indication, residual confounding, and maternal characteristics. The observed associations between methylphenidate and cardiovascular malformations and between exposure and low 5-minute Apgar score warrant continued investigation but should not be interpreted as evidence of causal harm.

PMID 42887725
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