Dexmethylphenidate

Dexmethylphenidate

Systematic (IUPAC) name
(R,R)-(+)-Methyl 2-phenyl-2-(2-piperidyl)acetate
Clinical data
Trade names	Focalin, Focalin XR, Attenade
AHFS/Drugs.com	monograph
MedlinePlus	a603014
Pregnancy cat.	C
Legal status	Controlled (S8) (AU) Schedule III (CA) Class B (UK) Schedule II (US)
Routes	oral
Pharmacokinetic data
Bioavailability	11 – 52%
Protein binding	30%
Metabolism	hepatic
Half-life	4 hours
Excretion	renal
Identifiers
CAS number	40431-64-9 N
ATC code	N06BA11
PubChem	CID 154101
DrugBank	DB06701
ChemSpider	135807 Y
UNII	M32RH9MFGP Y
KEGG	D07806 Y
ChEBI	CHEBI:51860 Y
ChEMBL	CHEMBL827 Y
Chemical data
Formula	C14H19NO2
Mol. mass	233.31 g/mol
SMILES O=C([C@@H]([C@@H]1NCCCC1)C2=CC=CC=C2)OC
InChI InChI=1S/C14H19NO2/c1-17-14(16)13(11-7-3-2-4-8-11)12-9-5-6-10-15-12/h2-4,7-8,12-13,15H,5-6,9-10H2,1H3/t12-,13-/m1/s1 Y Key:DUGOZIWVEXMGBE-CHWSQXEVSA-N Y
N (what is this?)  (verify)

Dexmethylphenidate, otherwise known as d-threo-methylphenidate (D-TMP), is the dextrorotatory enantiomer of methylphenidate. It is a norepinephrine-dopamine reuptake inhibitor (NDRI) and releasing agent and thus a psychostimulant, which affects the CNS. Dexmethylphenidate is sold as Focalin by Novartis, as Attenade by Celgene and as a generic drug by Teva, Mylan, and IntelliPharmaCeutics.^[1][2]

It is primarily used for the treatment of ADHD, for which it is generally effective and well-tolerated.^[3] Height and weight may be reduced by stimulant therapy in children, although this is not a major concern for most young people.^[4] Rarely, treatment emergent psychosis can occur during long-term therapy with dexmethylphenidate; regular psychiatric monitoring of people who are taking methylphenidate is recommended.^[5]

Medical uses

Dexmethylphenidate is used as a treatment for ADHD, usually along with psychological, educational, behavioral or other forms of treatment. It is proposed that stimulants help ameliorate the symptoms of ADHD by making it easier for the user to concentrate, avoid distraction, and control behavior. Dexmethylphenidate may also improve listening skills and organization of tasks, and may help prevent tic disorders. Because it is a psychostimulant, dexmethylphenidate may also help with narcolepsy and in certain cases of major depression.^{[citation needed]}

Efficacy

Placebo-controlled trials have shown that once-daily dexmethylphenidate XR was effective and generally well tolerated.^[3] Improvements in ADHD symptoms in children were significantly greater for dexmethylphenidate XR versus placebo.^[3] It also showed greater efficacy than osmotic release oral system (OROS) methylphenidate over the first half of the laboratory classroom day but assessments late in the day favoured OROS methylphenidate.^[3]

Adverse effects

Although the FDA has not concluded that psychostimulants increase the risk of cardiac problems in people without a heart condition, all psychostimulant labels include a warning stating that they may increase the risk of cardiovascular problems or sudden death.

Suicidal thinking has been reported in young people who are taking antidepressants at the same time they are taking an ADHD stimulant and many antidepressants carry a "black box warning" label concerning a possible increase in suicidal ideation in patients under 25 years of age.^[6]

Insomnia, dizziness, nausea, stomach pain, euphoria, headache, anxiety, anorexia, and weight loss are possible side effects of dexmethylphenidate.

On occasion, a treatment emergent psychosis can occur during long-term therapy with dexmethylphenidate. Stimulants such as dexmethylphenidate should be avoided in people who have a vulnerability to schizophrenia or drug addiction; however, psychotic symptoms may emerge during therapy with dexmethylphenidate in individuals without these risk factors; regular psychiatric monitoring of people who are taking dexmethylphenidate for adverse effects such as psychotic symptomatology (with regard to the need for dose adjustment or discontinuation of medication) has been recommended.^[7]

Height and weight may be reduced by stimulant therapy; this side effect may be dose dependent and children and adolescents catch up in growth overtime or after stopping stimulant therapy. For most young people effects of growth is not a major concern; nevertheless regular monitoring on height and weight by healthcare providers has been recommended.^[4]

Rare but more serious side effects include uncontrolled muscle movements (e.g., stiffness, twitching, shaking), hyperthermia, tics, edema of the feet/hands, blurred vision, mental/mood/behavior changes (e.g., agitation, aggression, mood swings, depression, hallucinations, abnormal thoughts/behavior), extreme tiredness, and severe sweating, easy bleeding/bruising, shortness of breath, fainting, chest/jaw/left arm pain, sudden vision changes, signs of infection (fever, persistent sore throat), tachycardia, weakness, seizures, confusion, slurred speech, and severe headaches and in some very rare cases death.^{[citation needed]}

Also, there is a potential for a severe allergic reaction, but it is extremely rare. Trouble breathing, itching, a rash, swelling, or dizziness are all signs/symptoms of this allergic reaction. ^{[citation needed]}

Interactions

Dexmethylphenidate should not be used by those who have taken a monoamine oxidase inhibitor (MAOI) such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) in the past 14 days. The use of dexmethylphenidate by a person chronically taking an MAOI is a medical emergency and should be treated immediately.^[8]

Mode of activity

Methylphenidate is a catecholamine reuptake inhibitor that indirectly increases catecholaminergic neurotransmission by inhibiting the dopamine transporter (DAT) and norepinephrine transporter (NET),^[9] which are responsible for clearing catecholamines from the synapse, particularly in the striatum and meso-limbic system.^[10] Moreover, it is thought to "increase the release of these monoamines into the extraneuronal space."^[11]

Although four stereoisomers of methylphenidate (MPH) are possible, only the threo diastereoisomers are used in modern practice. There is a high eudysmic ratio between the SS and RR enantiomers of MPH. "Dexmethylphenidate" is a preparation of the RR enantiomer of MPH.^[12][13] In theory, d-TMP can be anticipated to be twice the strength of the racemic product.^[14][9]

Pharmacology

Dexmethylphenidate has a 4-6 hour duration of effect (a long-acting formulation, Focalin XR, which spans 12 hours is also available and has been shown to be as effective as DL-TMP XR (Concerta, Ritalin LA), with flexible dosing and good tolerability.^[16][17]) It has also been demonstrated to reduce ADHD symptoms in both children^[18] and adults.^[19] d-MPH has a similar side-effect profile to MPH^[20] and can be administered without regard to food intake.^[21]

Dexmethylphenidate has a chemical structure similar to a family of key brain neurotransmitters called monoamines, which include norepinephrine and dopamine.^[22]

Typical daily doses of dexmethylphenidate are around 10–20 mg for children and 20–40 mg for adults. As with all psychostimulant compounds, some individuals may respond to a small dose while others will require a larger than average dose around 40–60 mg. Therefore, dosing is usually initiated at a typical range and then titrated to suit the patient.^[23]

Usage

The Focalin XR capsules are sometimes prescribed over other extended release stimulants because the capsules can be opened and their contents mixed with applesauce or pudding to help children who cannot, or will not, swallow large capsules. This is possible due to the SODAS (Spheroidal Oral Drug Absorption System) delivery system, also used in Ritalin LA. Focalin XR comes in five, ten, fifteen, twenty, thirty, and forty milligram capsules. To determine appropriate dosage doctors first prescribe one to four 5 mg capsules. An appropriate treatment plan is then based on the patient's reaction to the initial dose.^[24] From there, doctors usually increase the dose by 5 mg to 10 mg until finding the right dosage.

Legal status

Dexmethylphenidate, due to its abuse potential, is classed as a Schedule II controlled drug in the United States.^[25]

References

External links

• Information from the U.S. National Institute of Health