Top Gene Interactions
- Metabolism: Methylphenidate is hepatically metabolized. More specifically, it is rapidly and extensively metabolized by carboxylesterase CES1A1. Via this enzyme, methylphenidate undergoes de-esterification to ritalinic acid (a-phenyl-2-piperidine acetic acid, PPAA), which has little to no pharmacologic activity. Route of Elimination: After oral administration of an immediate release formulation of methylphenidate, 78%-97% of the dose is excreted in the urine and 1%-3% in the feces in the form of metabolites within 48-96 hours. Only small quantities (<1%) of unchanged methylphenidate appear in the urine. Most of the dose is excreted in the urine as ritalinic acid (60%-86%), the remainder being accounted for by minor metabolites. Half Life: d-methylphenidate = 3-4 hours; l-methylphenidate = 1-3 hours; Ritalinic acid = 3-4 hours;
- Uses/Sources: For use as an integral part of a total treatment program which typically includes other remedial measures (psychological, educational, social) for a stabilizing effect in children with a behavioral syndrome characterized by the following group of developmentally inappropriate symptoms: moderate-to-severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity.
- Health Effects: Using large amounts of these drugs can result in a condition known as amphetamine psychosis -- which can result in auditory, visual and tactile hallucinations, intense paranoia, irrational thoughts and beliefs, delusions, and mental confusion.
- Symptoms: Symptoms of overdose include vomiting, agitation, tremors, hyperreflexia, muscle twitching, convulsions (may be followed by coma), euphoria, confusion, hallucinations, delirium, sweating, flushing, headache, hyperpyrexia, tachycardia, palpitations, cardiac arrhythmias, hypertension, mydriasis, and dryness of mucous membranes.
- Treatment: Treatment consists of appropriate supportive measures. The patient must be protected against self-injury and against external stimuli that would aggravate overstimulation already present. Gastric contents may be evacuated by gastric lavage. In the presence of severe intoxication, use a carefully titrated dosage of a short-acting barbiturate before performing gastric lavage. Other measures to detoxify the gut include administration of activated charcoal and a cathartic. Intensive care must be provided to maintain adequate circulation and respiratory exchange; external cooling procedures may be required for hyperpyrexia. (L1712)
- Route of Exposure: Oral. Readily absorbed in a biphasic manner when orally administered (tablets) to children diagnosed with ADHD and to healthy adults. In children and adults males, after administration of a single oral dose of Ritalin LA and Ritalin given in two doses 4 hours apart, peak plasma concentration is reached approximately 2 hours for the first phase and 5-6 hours for the second phase. The absolute oral bioavailability of methylphenidate in children was 22±8% for d-methylphenidate and 5±3% for l-methylphenidate. These low values suggest that methylphenidate is highly metabolized presystemically.
- Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
- Toxicity: LD50: 190 mg/kg (oral, mice)
Mechanism of Action
|Target Name||Mechanism of Action||References|
Sodium-dependent serotonin transporter
Sodium-dependent dopamine transporter
Sodium-dependent noradrenaline transporter
|Methylphenidate blocks dopamine uptake in central adrenergic neurons by blocking dopamine transport or carrier proteins. Methylphenidate acts at the brain stem arousal system and the cerebral cortex and causes increased sympathomimetic activity in the central nervous system. Alteration of serotonergic pathways via changes in dopamine transport may result.||
Methylphenidate Interacts with Diseases
|Disease||Inference Score||References/Inference Genes|
|Congenital central hypoventilation syndrome||13.83||
|TOBACCO ADDICTION, SUSCEPTIBILITY TO||11.21||
|Attention deficit hyperactivity disorder||8.09||
|PARKINSON DISEASE, LATE-ONSET||7.83||
|Salivary gland neoplasm||7.73||
|HIV Wasting Syndrome||7.53||
|Wounds and Injuries||7.34||