Dexmethylphenidate (trade name Focalin, Novartis Novartis International AG is a multinational pharmaceutical company based in Basel, Switzerland, ranking number three in sales, which accounted 36.173 billon in 2008. It is currently the 6th largest Pharmaceutical company in terms of revenue with a profit margin of about 20%, which is the same as its industry competitors. Their profits were down, generic by Teva also available), otherwise known as d-threo-methylphenidate (D-TMP), is the dextrorotatory Dextrorotation and levorotation refer, respectively, to the properties of rotating plane polarized light clockwise (for dextrorotation) or counterclockwise (for levorotation), seen by an observer whom the light is approaching. A compound with dextrorotation is called dextrorotatory or dextrorotary, while a compound with levorotation is called enantiomer of methylphenidate Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, Postural Orthostatic Tachycardia Syndrome, and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult, obesity, and rarely other psychiatric disorders such as Obsessive-. It is a norepinephrine-dopamine reuptake inhibitor A norepinephrine-dopamine reuptake inhibitor is a drug which acts as a reuptake inhibitor for the neurotransmitters norepinephrine and dopamine by blocking the action of the norepinephrine transporter (NET) and the dopamine transporter (DAT), respectively. This in turn leads to increased extracellular concentrations of both norepinephrine and (NDRI) and thus a psychostimulant Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others. Due to their effects typically having an "up" quality to them, stimulants are also occasionally referred to as &, which affects the CNS The central nervous system is the part of the nervous system that coordinates the activity of all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish. It contains the majority of the nervous system and consists of the brain and the spinal cord, as well as.

Mode of activity

Methylphenidate is a catecholamine Catecholamines are sympathomimetic "fight-or-flight" hormones released by the adrenal glands in response to stress. They are part of the sympathetic nervous system reuptake inhibitor that indirectly increases catecholaminergic neurotransmission by inhibiting the dopamine transporter The dopamine transporter is a membrane-spanning protein that binds the neurotransmitter dopamine; DAT provides the primary mechanism through which dopamine is cleared from synapses, transporting dopamine from the synapse into a neuron. DAT is present in the peri-synaptic area of dopaminergic neurons in areas of the brain where dopamine signaling (DAT) and norepinephrine transporter The sodium-dependent noradrenaline transporter also known as the norepinephrine transporter or NET (or noradrenaline transporter ) is a monoamine transporter that transports the neurotransmitters norepinephrine (noradrenaline) and dopamine from the synapse back to its vesicles for storage until later use. NET is 617 amino acids in length, contains (NET), which are responsible for clearing catecholamines from the synapse In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell. The word "synapse" comes from "synaptein", which Sir Charles Scott Sherrington and colleagues coined from the Greek "syn-" and "haptein" ("to clasp"), particularly in the striatum The striatum, also known as neostriatum or striate nucleus, is a subcortical part of the forebrain. It is the major input station of the basal ganglia system. In primates (including humans), the striatum is divided by a white matter tract called the internal capsule into two sectors called the caudate nucleus and putamen and meso-limbic system The limbic system is a set of brain structures including the hippocampus, amygdala, anterior thalamic nuclei, and limbic cortex, which suggestively support a variety of functions including emotion, behavior, long term memory, and olfaction. The term "limbic" comes from the Latin limbus, for "border" or "edge". Some.^[1]

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.^[2][3] In theory, d-TMP can be anticipated to be twice the strength of the racemic product.^[4] However, certain authors recommend that the ratio is ~70% increase in potency upon enantiopurification of the racemate.^[5]

Therapeutic use

Dexmethylphenidate is used as a treatment for ADHD, ideally in conjunction 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 Narcolepsy is a chronic sleep disorder, or dyssomnia, characterized by excessive daytime sleepiness in which a person experiences extreme fatigue and possibly falls asleep at inappropriate times, such as while at work or at school. Narcoleptics usually experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which is often and in certain cases of major depression Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities. The term "major depressive disorder" was selected by the American Psychiatric Association to designate this symptom cluster as a mood disorder. Although its has many beneficial effects, because it is a stimulant there is a considerable chance for abuse of the drug. Doctors are advised to closely monitor a patient's intake of Dexmethlphenidate.

Importantly, the propensity for "abuse" with d-TMP is much less than for the corresponding racemic product.^[7]

Pharmacology

Dexmethylphenidate has a 4-6 hour duration of effect (a long-acting formulation, Focalin XR Dexmethylphenidate , otherwise known as d-threo-methylphenidate (D-TMP), is the dextrorotatory enantiomer of methylphenidate. It is a norepinephrine-dopamine reuptake inhibitor (NDRI) and thus a psychostimulant, which affects the CNS, 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.^[8][9]) It has also been demonstrated to reduce the symptoms of childhood ADHD,^[10] as well as ADHD in adults.^[11] d-MPH has a similar side-effect profile to MPH^[12] and can be administered without regard to food intake.^[13]

Dexmethylphenidate has a chemical structure similar to a family of key brain neurotransmitters called monoamines, which include norepinephrine and dopamine. The increase in dopamine which occurs with the use of this medication can create a sense of euphoria, and therefore may make the user subject to abuse of the drug.^[14]

Typical daily doses of dexmethylphenidate are around 10–20mg for children and 20–40mg for adults. As with all psychostimulant compounds, certain individuals may respond to a small dose and certain individuals may require a larger than average dose, hence, dosing is usually initiated at a typical range and then titrated to suit the patient.^[15]

There is a possibility of withdrawal symptoms if dexmethylphenidate use is discontinued suddenly. As with other stimulants, withdrawal symptoms may include emotional or behavioral depression. Tapering off is recommended, under the supervision of a doctor. Addiction The related concept of drug addiction has many different definitions. Some writers give in fact drug addiction the same meaning as substance dependence, others for example provide drug addiction a narrower meaning which excludes drugs without evidence of tolerance or withdrawal symptoms, which involves compulsive or harmful drug-seeking behavior, is rare but not impossible.^[16]

Efficacy

Placebo-controlled trials have shown that once-daily dexmethylphenidate XR was effective and generally well tolerated.^[17] Improvements in ADHD symptoms in children were significantly greater for dexmethylphenidate XR versus placebo. ^[17] 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. ^[17]

Concerns

The same concerns that apply to other stimulant drugs should be considered: Reports of sudden heart The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions. The term cardiac (as in cardiology) means "related to the heart" and comes from the Greek καρδιά, kardia, for "heart." death in children caused Canada to stop marketing Adderall Adderall is a brand-name psychostimulant medication composed of racemic amphetamine aspartate monohydrate, racemic amphetamine sulfate, dextroamphetamine saccharide and dextroamphetamine sulfate, which is thought to work by increasing the amount of dopamine and norepinephrine in the brain. Adderall is widely reported to increase alertness, libido, XR (another stimulant used to treat Attention-Deficit Hyperactivity Disorder Attention-Deficit Hyperactivity Disorder is a neurobehavioral developmental disorder. It is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone" and symptoms starting before seven years of age) for a period in 2005, however it was returned to the market in that same year after it was demonstrated that cardiac risk is low in patients free of congenital heart defects A congenital heart defect is a defect in the structure of the heart and great vessels of a newborn. Most heart defects either obstruct blood flow in the heart or vessels near it or cause blood to flow through the heart in an abnormal pattern, although other defects affecting heart rhythm (such as long QT syndrome) can also occur. Heart defects are. Heart problems have been reported, predominantly in young people taking ADD Attention-Deficit Hyperactivity Disorder is a neurobehavioral developmental disorder. It is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone" and symptoms starting before seven years of age stimulants, though the FDA The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments, responsible for protecting and promoting public health through the regulation and supervision of food safety, tobacco products, dietary supplements, prescription and over-the-counter has not concluded that psychostimulants increase risk of cardiac problems for a person without a heart condition. Suicidal thinking Suicidal ideation is a common medical term for thoughts about suicide, which may be as detailed as a formulated plan, without the suicidal act itself. Although most people who undergo suicidal ideation do not commit suicide, some go on to make suicide attempts. The range of suicidal ideation varies greatly from fleeting to detailed planning, role has been reported in young people who are taking antidepressants An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. Drugs including the monoamine oxidase inhibitors , tricyclic antidepressants (TCAs), tetracyclic antidepressants (TeCAs), selective serotonin reuptake inhibitors (SSRIs), and at the same time they are taking an ADHD stimulant and many antidepressants carry a "black box warning In the United States, a black box warning is a type of warning that appears on the package insert for prescription drugs that may cause serious adverse effects. It is so named for the black border that usually surrounds the text of the warning" label concerning a possible increase in suicidal ideation in patients under 18 years of age.^[18]

Side effects

Insomnia Insomnia is a symptom that can accompany several sleep, medical and psychiatric disorders, characterized by persistent difficulty falling asleep and/or difficulty staying asleep. Insomnia is typically followed by functional impairment while awake, nausea Nausea , is a sensation of unease and discomfort in the upper stomach with an urge to vomit. An attack of nausea is known as a qualm, stomach pain, euphoria Euphoria is medically recognized as a mental/emotional state defined as a profound sense of well-being. Some do not wish to admit that concepts such as 'euphoria' are essentially metaphysical. Technically, euphoria is an affect, but the term is often colloquially used to define emotion as an intense state of transcendent happiness combined with an, headache A headache or cephalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the pain-sensitive structures around the brain. Several areas of the, anxiety Anxiety is a psychological and physiological state characterized by cognitive, somatic, emotional, and behavioral components. These components combine to create an unpleasant feeling that is typically associated with uneasiness, apprehension, fear, or worry. Anxiety is a generalized mood condition that can often occur without an identifiable, anorexia Anorexia (deriving from the Greek "α-" (a(n)-, a prefix that denotes absence) + "όρεξη" (orexe) = appetite) is the decreased sensation of appetite. While the term in non-scientific publications is often used interchangeably with anorexia nervosa, many possible causes exist for a decreased appetite, some of which may be, and weight loss are common side effects.

Rare but much more serious side effects include uncontrolled muscle movements (e.g., stiffness, twitching, shaking), hyperthermia Hyperthermia is an elevated body temperature due to failed thermoregulation. Hyperthermia occurs when the body produces or absorbs more heat than it can dissipate. When the elevated body temperatures are sufficiently high, hyperthermia is a medical emergency and requires immediate treatment to prevent disability and death, tics A tic is a sudden, repetitive, nonrhythmic, stereotyped motor movement or vocalization involving discrete muscle groups. Tics can be invisible to the observer, such as abdominal tensing or toe crunching. Common motor and phonic tics are, respectively, eye blinking and throat clearing. Movements of other movement disorders must be distinguished, edema Edema or oedema (British English; both words from the Greek οἴδημα, oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body. Generally, the amount of interstitial fluid is determined by the balance of fluid homeostasis, and increased of the feet/hands, blurred vision, mental/mood/behavior changes (e.g., agitation, aggression In psychology, as well as other social and behavioral sciences, aggression refers to behavior between members of the same species that is intended to cause pain or harm. Predatory behavior between members of one species towards another species is also described as "aggression." To exhibit aggression towards members of another species is, mood swings, depression Depression is a state of low mood and aversion to activity. The Diagnostic and Statistical Manual of Mental Disorders defines a depressed person as experiencing feelings of sadness, helplessness and hopelessness. In traditional colloquy, feeling "depressed" is often synonymous with feeling "sad", but both clinical depression, hallucinations A hallucination, in the broadest sense of the word, is a perception in the absence of a stimulus. In a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid, substantial, and located in external objective space. The, abnormal thoughts/behavior), extreme tiredness, and severe sweating Perspiration is the production of a fluid consisting primarily of water as well as various dissolved solids (chiefly chlorides), that is excreted by the sweat glands in the skin of mammals. Sweat contains the chemicals or odorants 2-methylphenol (o-cresol) and 4-methylphenol (p-cresol), as well as a small amount of urea, easy bleeding/bruising, shortness of breath, fainting Syncope is the medical term for fainting, a sudden, usually temporary, loss of consciousness generally caused by insufficient oxygen in the brain either through cerebral hypoxia or through hypotension, but possibly for other reasons. Typical symptoms progress through dizziness, clamminess of the skin, a dimming of vision or brownout, possibly, chest/jaw/left arm pain, sudden vision changes, signs of infection (fever, persistent sore throat), tachycardia Tachycardia comes from the Greek words tachys and kardia (of the heart). Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heartrate (heartrate in an inactive or sleeping individual). It can be very dangerous depending on how hard the heart is working and the activity. The upper threshold of a normal human, weakness Weakness is a symptom used to describe a number of different conditions, including: lack of muscle strength, malaise, dizziness or fatigue. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, including muscular, seizures An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness. It can manifest as an alteration in mental state, tonic or clonic, confusion Confusion of a pathological degree usually refers to loss of orientation (ability to place oneself correctly in the world by time, location, and/or personal identity) sometimes accompanied by disordered consciousness and often memory (ability to correctly recall previous events or learn new material). Confusion as such is not synonymous with, slurred speech, and severe headaches and in some 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 severe dizziness are all signs/symptoms of this allergic reaction.^{[citation needed]}

Interactions

Dexmethylphenidate should not be used in combination with a monoamine oxidase inhibitor (MAOI) Monoamine oxidase inhibitors are a class of powerful antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression, and have also shown efficacy in smoking cessation such as isocarboxazid Isocarboxazid is an irreversible and nonselective monoamine oxidase inhibitor (MAOI) of the hydrazine chemical class used as an antidepressant and anxiolytic. It is one of the few hydrazine MAOIs still in clinical use, along with phenelzine (Marplan), phenelzine Phenelzine is a non-selective and irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class which is used as an antidepressant and anxiolytic. Along with tranylcypromine and isocarboxazid, phenelzine is one of the few non-selective MAOIs still in widespread clinical use (Nardil), rasagiline Rasagiline is an irreversible inhibitor of monoamine oxidase used as a monotherapy in early Parkinson's disease or as an adjunct therapy in more advanced cases. It is selective for MAO type B over type A by a factor of fourteen (Azilect), selegiline Selegiline is a drug used for the treatment of early-stage Parkinson's disease, depression and senile dementia. In normal clinical doses it is a selective irreversible MAO-B inhibitor, however in larger doses it loses its specificity and also inhibits MAO-A. Dietary restrictions are common for MAOI treatments, but special dietary restrictions for (Eldepryl, Emsam), or tranylcypromine Tranylcypromine is a drug of the substituted phenethylamine and amphetamine classes which acts as a monoamine oxidase inhibitor (MAOI)—it is a non-selective and irreversible inhibitor of the enzyme monoamine oxidase (MAO). It is used as an antidepressant and anxiolytic agent in the clinical treatment of mood and anxiety disorders, respectively (Parnate) that has been used in the past 14 days. Serious, life-threatening side effects can occur if dexmethylphenidate is taken with an MAOI.

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 come in five, ten, fifteen, and twenty 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. ^[19] From there, doctors usually increase dose from 5 mg to 10 mg until finding the right dosage.

Legal status

Dexmethylphenidate, due to its abuse potential is classed as a Schedule II Drug prohibition law is prohibition-based law by which governments prohibit, except under licence, the production, supply, and possession of many, but not all, substances which are recognised as drugs, and which corresponds to international treaty commitments in the Single Convention on Narcotic Drugs 1961, the Convention on Psychotropic controlled drug in the United States.^[20]

External links

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

References

1. ^ Schweri, MM; Skolnick, P; Rafferty, MF; Rice, KC; Janowsky, AJ; Paul, SM (1985). "3HThreo-(+/-)-methylphenidate binding to 3,4-dihydroxyphenylethylamine uptake sites in corpus striatum: correlation with the stimulant properties of ritalinic acid esters". Journal of neurochemistry 45 (4): 1062–70. doi:10.1111/j.1471-4159.1985.tb05524.x. PMID 4031878.
2. ^ Ding, YS; Fowler, JS; Volkow, ND; Dewey, SL; Wang, GJ; Logan, J; Gatley, SJ; Pappas, N (1997). "Chiral drugs: comparison of the pharmacokinetics of 11Cd-threo and L-threo-methylphenidate in the human and baboon brain". Psychopharmacology 131 (1): 71–8. doi:10.1007/s002130050267. PMID 9181638.
3. ^ Ding, Y.; Gatley, S.; Thanos, P.; Shea, C.; Garza, V.; Xu, Y.; Carter, P.; King, P. et al. (2004). "Brain kinetics of methylphenidate (Ritalin) enantiomers after oral administration". Synapse (New York, N.Y.) 53 (3): 168–175. doi:10.1002/syn.20046. PMID 15236349.
4. ^ Davids, E.; Zhang, K.; Tarazi, F.; Baldessarini, R. (2002). "Stereoselective effects of methylphenidate on motor hyperactivity in juvenile rats induced by neonatal 6-hydroxydopamine lesioning". Psychopharmacology 160 (1): 92–98. doi:10.1007/s00213-001-0962-5. PMID 11862378.
5. ^ Markowitz, J.; Patrick, K. (2008). "Differential pharmacokinetics and pharmacodynamics of methylphenidate enantiomers: does chirality matter?". Journal of clinical psychopharmacology 28 (3 Suppl 2): S54–S61. doi:10.1097/JCP.0b013e3181733560. PMID 18480678.
6. ^ Williard, R.; Middaugh, L.; Zhu, H.; Patrick, K. (2007). "Methylphenidate and its ethanol transesterification metabolite ethylphenidate: brain disposition, monoamine transporters and motor activity". Behavioural pharmacology 18 (1): 39–51. doi:10.1097/FBP.0b013e3280143226. PMID 17218796.
7. ^ U.S. Patent 5,908,850
8. ^ Mcgough, J.; Pataki, C.; Suddath, R. (2005). "Dexmethylphenidate extended-release capsules for attention deficit hyperactivity disorder". Expert review of neurotherapeutics 5 (4): 437–441. doi:10.1586/14737175.5.4.437. PMID 16026226.
9. ^ Silva, R.; Tilker, H.; Cecil, J.; Kowalik, S.; Khetani, V.; Faleck, H.; Patin, J. (2004). "Open-label study of dexmethylphenidate hydrochloride in children and adolescents with attention deficit hyperactivity disorder". Journal of child and adolescent psychopharmacology 14 (4): 555–563. doi:10.1089/cap.2004.14.555. PMID 15662147.
10. ^ Arnold, L.E., et al. (2004). "A double-blind, placebo-controlled withdrawal trial of dexmethylphenidate hydrochloride in children with attention deficit hyperactivity disorder". J Child Adolesc Psychopharmacol. 2004 Winter;14(4):542-54.
11. ^ Spencer, T.; Adler, L.; Mcgough, J.; Muniz, R.; Jiang, H.; Pestreich, L.; Adult Adhd Research, G. (2007). "Efficacy and safety of dexmethylphenidate extended-release capsules in adults with attention-deficit/hyperactivity disorder". Biological psychiatry 61 (12): 1380–1387. doi:10.1016/j.biopsych.2006.07.032. PMID 17137560.
12. ^ Keating, GM; Figgitt (2002). "Dexmethylphenidate". Drugs 62 (13): 1899–904; discussion 1905–8. doi:10.2165/00003495-200262130-00009. PMID 12215063.
13. ^ Teo, S.; Scheffler, M.; Wu, A.; Stirling, D.; Thomas, S.; Stypinski, D.; Khetani, V. (2004). "A single-dose, two-way crossover, bioequivalence study of dexmethylphenidate HCl with and without food in healthy subjects". Journal of clinical pharmacology 44 (2): 173–178. doi:10.1177/0091270003261899. PMID 14747426.
14. ^ "[1]".
15. ^ Quinn, D. (2008). "Does chirality matter? Pharmacodynamics of enantiomers of methylphenidate in patients with attention-deficit/hyperactivity disorder". Journal of clinical psychopharmacology 28 (3 Suppl 2): S62–S66. doi:10.1097/JCP.0b013e3181744aa6. PMID 18480679.
16. ^ "Oral Uses".
17. ^ ^{a b c} Moen M, Keam S.Dexmethylphenidate Extended Release: A Review of its Use in the Treatment of Attention-Deficit Hyperactivity Disorder. CNSDrugs 2009; 23(12):1057-1083.doi:10.2165/11201140-000000000-00000.
18. ^ Rader, R; Mccauley, L; Callen, EC (2009). "Current strategies in the diagnosis and treatment of childhood attention-deficit/hyperactivity disorder". American family physician 79 (8): 657–65. PMID 19405409.
19. ^ "Focalin XR for ADHD".
20. ^ "Dexmethylphenidate--Novartis/Celgene. Focalin, D-MPH, D-methylphenidate hydrochloride, D-methylphenidate, dexmethylphenidate, dexmethylphenidate hydrochloride". Drugs in R&D 3 (4): 279–82. 2002. PMID 12455205.

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