Methylphenidate metabolism

Methylphenidate Metabolism. The metabolism and pharmacokinetics of methylphenidate have been studied extensively. Methylphenidate (8)is administered as the racemic threo isomer, but the (-)-threo enantiomer is more rapidly metabolized. 

Several classes of drugs modulate the firing rates or patterns of midbrain dopamine neurons by direct, monosynaptic, or indirect, polysynaptic, inputs to the cell bodies within the ventral mesencephalon (i.e., nicotine and opiates). In contrast, amphetamine, cocaine, and methylphenidate act at the level of the dopamine terminal interfering with normal processes of transmitter packaging, release, reuptake, and metabolism. 

Amantidine, bromocriptine, mazindol, pergolide, cabergoline, L-dopa/carbidopa, pramipexole, ABT-431, catecholamine metabolism inhibitors (disulfiram, phenelzine, selegiline), amineptine Methylphenidate, /-amphetamine, tropanes, GBR-12909 (partial agonist that may also act as antagonist), modafinil, coca tea... 

CNS stimulants can be classified as Psychomotor stimulants compounds that display a stimulatory effect primarily on brain functions and which activate mental and physical activity of the organism. They are made up of methylxanthines (caffeine, theophylline, pentoxifyllin), amphetamines (dextroamphetamine, methamphetamine), and also methylphenidate and pemoline. Respiratory stimulants or analeptics compounds, which cause certain activations of mental and physical activity of the organism, and primarily excite the vasomotor and respiratory centers of the medulla (doxapram, almitrine).Drwgi that suppress appetite or anorectics drags that activate mental and physical activity of the organism, but primarily accentuate the excitatory center of satiation in the hypothalamus (phentermine, diethylpropion).In order to increase mental capability, nootropics — drugs that increase the functional state of the brain — are sometimes used, the effect of which is associated with blood flow and metabolism of the brain. 

Mefabo//sm - Methylphenidate is metabolized rapidly primarily via deesterification to alpha-phenyl-piperidine acetic acid (PPA or ritalinic acid). The metabolite has little or no pharmacologic activity. 

Methylphenidate is an inhibitor of drug metabolizing enzymes of the cytochrome P450 family and several interactions with drugs like some antiepileptics, antidepressants and oral anticoagulants, have been described. 

Dexedrine, methylphenidate Inhibition of metabolism at 2D6 enzyme seen in vitro Potential TCA toxicity, none reported in literature Currently theoretical interaction only Fawcett, 2000... 

Methylphenidate hydrochloride, a piperidine derivative structurally similar to amphetamine, is a commonly prescribed stimulant for the treatment of ADHD in children age 6 years and older. It is a racemic mixture of d,l methyl a-phenyl-2-piperidineacetate hydrochloride. The drug is available in immediate-release, extended-release, and controlled-release formulations. It is hepatically metabolized to an inactive metabolite and excreted by the kidneys. 

Methylphenidate is chemically and pharmacologically similar to amphetamine. Both act by releasing norepinephrine and dopamine in brain. Both produce increased mental activity with little action on central and peripheral functions. It is well absorbed orally, metabolized and excreted in urine. 

Porrino, L., 6c Lucignani, G. (1987). Different patterns of local brain energy metabolism associated with high and low doses of methylphenidate Relevance to its action in hyperactive children. Biological Psychiatry, 22, 126-128. 

Volkow, N., Wang, G., Fowler, J., Logan, J., Angrist, B., Hitzemann, R., et al. (1997). Effects of methylphenidate on regional brain glucose metabolism in humans Relationship to dopamine D2 receptors. American Journal of Psychiatry, 154, 50-55. 

The interaction with methylphenidate may be of particular significance, because of claims that tricyclic antidepressants and methylphenidate have a synergistic effect on mood, owing to interference by methylphenidate with the metabolism of imipramine, resulting in increased blood imipramine concentrations (182). The occurrence of this hypertensive interaction calls for caution in the use of such combinations, for which there is no established evidence. 

SYMPATHOMIMETICS CYTOTOXICS -PROCARBAZINE Co-administration of ephedrine, metaraminol, methylphenidate, phenylephrine or pseudoephedrine (including nasal and ophthalmic solutions) with procarbazine may cause a prolongation and t intensity of the cardiac stimulant effects and effects on BP, which may lead to headache, arrhythmias, hypertensive or hyperpyretic crisis The metabolism of sympathomimetics is impaired due to an inhibition of MAO It is recommended that sympathomimetics not be administered during and within 14 days of stopping procarbazine. Do not use any OTC nasal decongestants (sprays or oral preparations) or asthma relief agents without consulting the pharmacist/doctor... 

INDIRECT TCAs 1. Methylphenidate T TCA levels, which may improve their efficacy, but cases of toxicity with imipramine have been reported 2. TCAs possibly 1 efficacy of indirect sympathomimetics 1. Uncertain postulated to be due to inhibition of the hepatic metabolism of TCAs 2. Indirect sympathomimetics cause release of norepinephrine from the nerve endings this is blocked by TCAs 1. Warn patients to watch for early signs of t TCA efficacy such as drowsiness and dry mouth 2. Watch for poor response to indirect sympathomimetics... 

DEXAMFET AMINE, METHYLPHENIDATE DISULFIRAM Risk of psychosis Additive effects these drugs interfere with dopamine metabolism Caution with co-administration. Warn patients and carers to watch for early features... 

This drug is a central nervous system stimulant that is considered to prevent the reuptake of norepinephrine and dopamine into the presynaptic neurones and increase the release of these neurotransmitters to the extraneuronal space. A high-fat meal increases its absorption. Methylphenidate in animal experiments was found to inhibit CYP1A and CYP2E1 by 50%. It is metabolized by de-esterification to inactive metabolites. 

Fluoxetine, paroxetine, bupropion, duloxetine, and other CYP450 2D6 inhibitors may increase TCA concentrations Cimetidine may increase plasma concentrations of TCAs and cause anticholinergic symptoms Phenothiazines or haloperidol may raise TCA blood concentrations May alter effects of antihypertensive drugs may inhibit hypotensive effects of clonidine Use of TCAs with sympathomimetic agents may increase sympathetic activity Methylphenidate may inhibit metabolism of TCAs... 

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