Dexmethylphenidate
4 sources
🧬 Receptor activity
| Target | Action | Affinity | Source | |
|---|---|---|---|---|
| Sodium-dependent dopamine transporter | — | Ki 74.6 nM | CHEMBL | TargetSodium-dependent dopamine transporter Action— AffinityKi 74.6 nM SourceCHEMBL |
| Norepinephrine transporter | — | Ki 270 nM | CHEMBL | TargetNorepinephrine transporter Action— AffinityKi 270 nM SourceCHEMBL |
| Unchecked | — | Ki 10000 nM | CHEMBL | TargetUnchecked Action— AffinityKi 10000 nM SourceCHEMBL |
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.
Pharmacokinetics
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.
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.
Dexmethylphenidate is mainly eliminated renally. After 48 hours, 90% of the dose is collected in the urine and 3.3% is collected from feces.
2.65L/kg when administered intravenously.
0.40L/hr/kg following an intravenous dose and a renal clearance of 0.005L/hr/kg.
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.
epatic, methylphenidate is metabolized primarily by de-esterification to ritalinic acid (α-phenyl-2-piperidine acetic acid, PPAA), which has little to no pharmacologic activity.
Route of Elimination: Renal
Half Life: 2-4 hours
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.
External links
Fact-sheets from PsychonautWiki. Harm-reduction reference only — not medical advice.