Objective: The abuse potential of methylphenidate has been related to the drug's capacity to produce a rapid onset of blockade of the presynaptic dopamine transporter in the brain. An oral once-a-day osmotic controlled-release formulation of methylphenidate produces a more gradual rise in plasma methylphenidate concentration, compared with immediate-release methylphenidate. The authors hypothesized that osmotic-release methylphenidate would also produce a slower onset of blockade of the presynaptic dopamine transporter and would be associated with a lower risk for detection and likeability, compared to immediate-release methylphenidate.
Method: Twelve healthy adults were randomly assigned to receive single doses of immediate-release methylphenidate or osmotic-release methylphenidate. Doses predicted to produce equivalent maximum concentration (C(max)) values were selected (40 mg of immediate-release methylphenidate and 90 mg of osmotic-release methylphenidate). Plasma d-methylphenidate levels and responses to detection/likeability questionnaire items were obtained hourly for 10 hours after administration of methylphenidate on two separate occasions for each subject. Dopamine transporter receptor occupancies were measured at hours 1, 3, 5, and 7 by using a carbon-11-labeled imaging agent (Altropane) and positron emission tomography.
Results: Despite similar C(max) values for both formulations, osmotic-release methylphenidate was associated with a longer time to maximum concentration, longer time to maximum CNS dopamine transporter occupancy, and no detection/likeability, compared with immediate-release methylphenidate.
Conclusions: The findings suggest that the abuse potential of oral methylphenidate is strongly influenced by the rate of delivery and not solely by the magnitude of plasma concentration or brain transporter occupancy. These results advance understanding of the underlying central effects of methylphenidate in humans and identify a potentially less abusable methylphenidate formulation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1176/appi.ajp.163.3.387 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Background: The locus coeruleus (LC), is the first brain region to develop hyperphosphorylated tau (ptau) inclusions in Alzheimer's disease (AD) and undergoes catastrophic degeneration in later stages of the disease. Importantly, the LC is the main noradrenergic nucleus in the brain and source of NE in the forebrain, and dysregulation of the neurotransmitter norepinephrine (NE) is associated with AD symptoms, as its release in the forebrain regulates attention, arousal, stress response, and learning and memory. Moreover, the LC may transmit pathogenic tau to the forebrain via its extensive projections.
View Article and Find Full Text PDFClinical Manifestations.
Alzheimers Dement
December 2024
Case Western Reserve University, Cleveland, OH, USA.
Background: A patient presented to movement disorder clinic with cognitive complaints, imbalance and prior diagnosis of NPH. The patient underwent ventriculoperitoneal shunt in the past with minimal improvement, a detailed history is suggestive of REM sleep behavioral disorder, autonomic dysfunction including orthostatic hypotension and urinary incontinence.
Method: Clinical evaluation was notable for bradykinesia, rigidity, truncal and cervical dystonia, shuffling steps, reduced arm swing bilaterally and pink, dusky skin of both hands.
Drug inhibition and substrate transport mechanisms of human VMAT2.
Nat Commun
January 2025
Shanghai Fifth People's Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Vesicular monoamine transporter 2 (VMAT2) is crucial for packaging monoamine neurotransmitters into synaptic vesicles, with their dysregulation linked to schizophrenia, mood disorders, and Parkinson's disease. Tetrabenazine (TBZ) and valbenazine (VBZ), both FDA-approved VMAT2 inhibitors, are employed to treat chorea and tardive dyskinesia (TD). Our study presents the structures of VMAT2 bound to substrates serotonin (5-HT) and dopamine (DA), as well as the inhibitors TBZ and VBZ.
View Article and Find Full Text PDFLongitudinal Trajectory of Dopamine and Serotonin Transporters in Parkinson Disease.
J Nucl Med
January 2025
Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
Parkinson disease (PD) is a multisystem disorder marked by progressive dopaminergic neuronal degeneration in the substantia nigra, as well as nondopaminergic systems. Our aim was to investigate longitudinal changes in -(3-[F]fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (F-FP-CIT) binding at the putamen, substantia nigra, and raphe nuclei in PD. This retrospective cohort study enrolled 127 patients with PD, who underwent F-FP-CIT PET scans twice or more, and 71 age- and sex-matched healthy controls.
View Article and Find Full Text PDFUse of the specific binding ratio distribution to characterise multiple system atrophy in advanced iodine-123-labelled N-(3-fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane serotonin transporter imaging.
Asia Ocean J Nucl Med Biol
January 2025
Department of Radiology, Fujita Health University School of Medicine, Aichi, Japan.
Objectives: Sudden death in multiple system atrophy (MSA) is caused by decreased serotonergic innervation, but there is no routine test method for this decrease. In addition to dopamine transporters, iodine-123-labelled N-(3-fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (I-FP-CIT) binds serotonin transporters (SERTs). We noted a binding potential to quantify the total quantity of I-FP-CIT binding to its receptors.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!