methylphenidate solution / Generic mfg. - LARVOL DELTA

[VIRTUAL] Non-prescripted usage of psychostimulant drugs by medical students (EAN 2020) - "Among the study group 64% were using methylphenidate, 14% modafinil and 21% were using both. Our study has shown that stimulant usage increases in the course of medical education. However stimulants don’t have any positive effects on GPA. We advocate more research in this area to expose the extent of the problem and begin to explore potential solutions for study habits and lifestyle choices."

Attention Deficit Hyperactivity Disorder • CNS Disorders

Solid phase microextraction combined with thermal-desorption electrospray ionization mass spectrometry for high-throughput pharmacokinetics assays. (PubMed, Anal Chim Acta) - "Methylphenidate in plasma was extracted and concentrated by direct immersion SPME using fused-silica fibers coated with polydimethylsiloxane. As a viable alternative to LC-MS, SPME-TD-ESI/MS enables simple, rapid, and high-throughput analysis of drugs in plasma. The developed approach is particularly beneficial to PK studies for a very small sample volume (10 μL) is needed, the extraction time is as short as 3 min, and the detection time is less than 30 s."

Journal • PK/PD data • Biosimilar

Identifying PET imaging biomarkers of alpha-synuclein pathology (Neuroscience 2017) - "Dynamic PET scans were performed with 11CPIB, 11C-methylphenidate, 11C-DTBZ and 11C-raclopride 1, 3, 5 and 9 month (m) after injection and the animals were sacrificed after each time point. Our next steps include the comparison of Kd values from the tritiated compounds to Aβ and τ fibrils to confirm αSYN selectivity. In addition, PET tracers from the two best compounds will be developed and tested in vivo."

Parkinson's Disease

Use of UPLC-HRMS/MS for In Vitro and In Vivo Metabolite Identification of Three Methylphenidate-derived New Psychoactive Substances. (PubMed, J Anal Toxicol) - "pS9 incubations additionally indicated that all investigated substances were primarily hydrolyzed, resulting in the corresponding carboxy metabolites. Finally, these carboxy metabolites should be used as additional analytical targets besides the parent compounds for comprehensive mass spectrometry-based screening procedures."

Journal • Preclinical

4-Fluoromethylphenidate: Fatal Intoxication Involving a Previously Unreported Novel Psychoactive Substance in the USA. (PubMed, J Anal Toxicol) - "In addition to the detection of 4F-MPH, 3-methoxy-PCP, amphetamine, methamphetamine, 6-monoacetylmorphine, morphine, codeine and tetrahydrocannabinol were also identified in the decedent. This peak suggests the presence of a structural isomer, possibly (±)-erythro-4-fluoromethylphenidate, which cannot be confirmed due to there being no available certified reference material. This case report presents the first time that 4F-MPH was detected in a decedent, as well as the first time 4F-MPH has been listed in the official cause of death of a decedent in Florida."

Journal

The Effects of Methylphenidate on Creativity in Individuals with Attention Deficit Hyperactivity Disorder (AAN 2020) - "It appears that MPH does not impair creativity in ADHD patients, and overall, increases semantic fluency. Further exploration is needed with an expanded sample size to confirm the opposing effects of MPH on fluency and problem solving."

Clinical

Postmortem Brain-Blood Ratios of Amphetamine, Cocaine, Ephedrine, MDMA and Methylphenidate. (PubMed, J Anal Toxicol) - "The metabolite of cocaine, benzoylecgonine, was also quantified in brain and blood from 60 cases, and the median brain-blood ratio was 0.66 with 10-90 percentiles of 0.39-1.27. The results of this study can aid the toxicological investigation in determining the cause of death."

Journal

Analytically Confirmed Intoxication by 4-Fluoromethylphenidate, an Analog of Methylphenidate. (PubMed, J Anal Toxicol) - "The patient required sedation with intravenous diazepam and was discharged two days later with a prescription of promazine and quetiapine. Analyses for classic drugs (opiates, methadone, cocaine, cannabis metabolites, amphetamines, ecstasy and LSD), ethanol, qualitative full screen by gas chromatography-mass spectrometry and targeted analysis for 50 NPS by liquid chromatography-tandem mass spectrometry tested negative; comorbidities were excluded, too. Based on these data, it can be assumed that the clinical manifestations were due to 4F-MPH only."

Journal

Long-term challenge of methylphenidate changes the neuronal population and membrane property of dopaminergic neuron in rats. (PubMed, Neurochem Int) - "Furthermore, the amplitude of action potential of the dopaminergic neurons with slow firing was higher in the High-dose group than those in the Normal and Low-dose groups. The firing behavior of dopaminergic neurons and dopamine concentration in the brain is affected by the long-term challenge of methylphenidate."

Journal

Mechanism of Action of DELEXIS(r), a Novel, Oral, Colonic-Targeted Drug Delivery Platform (APSARD 2020) - "Evening-dosed JORNAY PM(TM), a DR and ER methylphenidate (DR/ER-MPH), utilized the DELEXIS drug delivery platform to target onset of effect coinciding with awakening and lasting into the evening. The PK profile of DR/ER-MPH supports the use of DELEXIS as a novel, oral, colonic-targeted, DR and ER drug delivery platform that provides a consistent time to onset of drug absorption and a prolonged drug release over an extended period. Low inter-subject and intra-subject variability suggest that the optimal titration of DR/ER-MPH will result in a consistent absorption profile."

A Phase 4, Open-Label, Single-Dose Pharmacokinetic Study of a Novel Methylphenidate Extended-Release Orally Disintegrating Tablet Formulation in Preschool-Aged Children (APSARD 2020) - "MPH XR-ODT was well tolerated in preschool-aged children. Peak plasma concentration of and exposure to d-MPH were significantly greater than those of l-MPH, and d‑MPH had a longer half-life, consistent with previous studies of oral MPH."

Clinical • P4 data • PK/PD data

An In Vitro/In Vivo Correlation (IVIVC) Model for HLD200, an Evening-Dosed Delayed-Release and Extended-Release Methylphenidate (APSARD 2020) - "A successful convolution-based Level A IVIVC model for DR/ER-MPH was developed and validated."

Preclinical

In Vitro Dissolution and in Vivo Absorption of Methylphenidate from a Delayed-Release and Extended-Release Drug Delivery Platform (APSARD 2020) - "HLD200 is the first and only evening-dosed delayed-release and extended-release methylphenidate (DR/ER-MPH), which utilizes a novel drug delivery platform (DELEXIS®) designed to delay initial drug release 8–10 hours to target an onset of therapeutic effect with awakening and lasting into the evening. Because of its targeting to the less absorptive colon, DR/ER-MPH exhibits a biological lag compared to OROS MPH, with MPH being absorbed at a much slower rate than it is released. Owing to this biological lag, DR/ER-MPH exhibits a protracted elimination phase compared to OROS MPH, with ~50% of MPH exposure occurring after peak plasma concentrations of MPH are reached. The non-linear IVIVC of DR/ER-MPH is uncharacteristic for BCS class 1 or 2 compounds."

Preclinical

Modeling the effects of methylphenidate on interference and evidence accumulation processes using the conflict linear ballistic accumulator. (PubMed, Psychopharmacology (Berl)) - "Enhancement of evidence accumulation is a biologically plausible and task-general mechanism of stimulant effects on cognition. Moreover, the assumption that methylphenidate's effects on behavior are only visible with complex executive tasks may be misguided."

Journal

Spectrum of acute drug toxicity during the most popular house and techno party in the world. (EUSEM 2019) - "The three leading drugs were cocaine (21.3%), 3,4-methylenedioxymethamphetamine (MDMA) (19.1%) and tetrahydrocannabinol (THC) (17.0%) followed by methamphetamine (8.5%), methylphenidate (6.4%) and 2.1% for each lysergic acid diethylamide and amphetamine. Cocaine, MDMA and THC in combination with alcohol are the most prevalent drugs in Street Parade patients whereas NPS are still rare. Methamphetamine intoxications seem to increase. Thus, future preventive strategies need to sensitize the rave scene about the drug spectrum and possible health consequences."

A Prospective Open-Label Trial of Long-Acting Liquid Methylphenidate for the Treatment of Attention Deficit/Hyperactivity Disorder in Intellectually Capable Adults with Autism Spectrum Disorder. (PubMed, World J Biol Psychiatry) - P4; " Our findings suggest that MPH-ER is effective and well-tolerated in the treatment of ADHD in HF-ASD adults."

Clinical • Journal

The effects of dopaminergic psychostimulants on complex problem solving (Neuroscience 2019) - "Participants received 15 mg dextroamphetamine, 30 mg methylphenidate, 200 mg modafinil, or placebo, counterbalanced across 4 testing sessions. Performance in the Knapsack Task correlated strongly with the CANTAB Spatial Working Memory Task strategy score.These findings suggest that dopaminergic stimulant medications may increase healthy adults’ motivation to spend more time and explore more combinations in pursuit of the solution to a computationally complex problem. However, this does not always result in enhanced performance because exploration becomes more random, which decreases performance."

Corneal Edema Associated With Systemic Dopaminergic Agents. (PubMed, Cornea) - "Methylphenidate, ropinirole, and resiniferatoxin have different mechanisms of actions but have a common end point leading to increased dopamine. We believe that these agents are linked with the reversible corneal edema seen in our 3 patients. This strongly correlates with previous studies that have linked amantadine, a drug that blocks dopamine reuptake, to reversible corneal edema."

Journal

Filamentary Keratitis After Amantadine Treatment in a Man with Acute Disseminated Encephalomyelitis: A Case Report (AAPMR 2019) - "He was continued on lubrifresh ointment for dry eyes, and started on methylphenidate with the goals of improving processing speed, attention, and memory. Conclusion : Amantadine continues to be frequently used in patients recovering from brain injuries. Serious ocular side effects to amantadine should be considered in patients presenting with ocular complaints while on this medication, particularly if renal clearance is compromised."

Clinical

Regulatory effect of Shudihuang on expressions of BDNF/TrkB and NRG-3 in prefrontal cortex and striatum of ADHD model rats (PubMed, Zhongguo Zhong Yao Za Zhi) - "Thirty 4-week-old spontaneous hypertension rats (SHR) were randomly divided into model group, methylphenidate hydrochloride (MPH, 2 mg·kg⁻¹·d⁻¹) and Shudihuang group (2.4 g·kg⁻¹·d⁻¹). Four weeks later after administration, both Shudihuang and MPH significantly elevated mRNA and protein expressions of BDNF/TrkB and NRG-3 (P<0.05).In conclusion, neurodevelopmental disorder mediated by BDNF/TrkB and NRG-3 was closely related with SHR rats' behaviors. Shudihuang may ameliorate the spontaneous and impulsive behaviors by up-regulating the expressions of BDNF/TrkB and NRG-3 and improving growth and maturation of neurons in SHR."

Journal

The system-neurophysiological basis for how methylphenidate modulates perceptual-attentional conflicts during auditory processing. (PubMed, Hum Brain Mapp) - "These modulations were further shown to be associated with activation differences in the temporoparietal junction (BA40) and the superior parietal cortex (BA7) and may reflect neuronal gain modulation principles. The findings provide mechanistic insights into the role of modulated dopamine/norepinephrine transmitter systems for the interactions between perception and attention."

Journal

Recreational drug use at a major music festival: trend analysis of anonymised pooled urine. (PubMed, Clin Toxicol (Phila)) - "Widespread uses of classical recreational drugs were identified in pooled urine samples. The prevalence of NPS was not as comprehensive as expected based on the European and Danish health authorities reports on illegal drugs. Urine drug-screening immunoassays results are advised to be confirmed by chromatographic bioanalysis."

Journal

Mass Spectrometry Imaging Shows Cocaine and Methylphenidate have Opposite Effects on Major Lipids in Drosophila Brain. (PubMed, ACS Chem Neurosci) - "When the lipid changes caused by cocaine were compared with those induced by methylphen-idate, it was shown that these drugs exert opposite effects on the brain lipid structure. We speculate that this might relate to the molecular mechanism of cognition and memory."

Journal

Corbicula fluminea rapidly accumulate pharmaceuticals from an effluent dependent urban stream. (PubMed, Chemosphere) - "Acetaminophen, caffeine, carbamazepine, diltiazem, diphenhydramine, fluoxetine, norfluoxetine, sertraline, desmethylsertraline, and methylphenidate were identified in C. fluminea whole body tissue homogenates via isotope dilution liquid chromatography-tandem mass spectrometry. Notably, elevated bioaccumulation factors (L/kg) for sertraline were observed between 3361 and 6845, which highlights the importance of developing predictive bioaccumulation models for ionizable contaminants with bivalves. Future research is also necessary to understand different routes of exposure and elimination kinetics for pharmaceutical accumulation in bivalves."

Journal

Relief From Two Courses of Intravenous Ketamine in a Patient With Medication- and Transcranial Magnetic Stimulation-Resistant Bipolar Depression (APA 2019) - "The patient failed multiple psychotropic medication trials, including sertraline, fluoxetine, escitalopram, lamotrigine, risperidone, dexmethylphenidate, amphetaminedextroamphetamine, lisdexamfetamine, methylphenidate, and guanfacine. With limited data on the serial use of ketamine infusions, such a regimen should be approached with great caution until safety and efficacy data are available on longer-term use of ketamine infusions. Further investigation is needed regarding the safety of long-term ketamine use in a controlled clinical setting."

Clinical