Methylphenidate

Ritalin, the trademarked name of methylphenidate, is commonly prescribed to children ages 7–18 with attention-deficit hyperactivity disorder.

Methylphenidate is a mild stimulant prescribed to individuals (usually for children, and sometimes controversially) who have behavioral problems characterized by hyperactivity and short attention span. The National Institute of Mental Health estimates that approximately 3–5 percent of the general population has attention-deficit disorder (ADD) or attention-deficit hyperactivity disorder (ADHD). The administration of methylphenidate to children diagnosed with hyperactivity and/or attention-deficit disorder can have a calming effect on the children and can enable them to focus on schoolwork. Methylphenidate is also used to treat narcolepsy, a sleep disorder characterized by a permanent and overwhelming feeling of sleepiness and fatigue.

Methylphenidate is similar to amphetamine and, like amphetamine, stimulates the central nervous system (CNS), which consists of the brain and spinal cord. Stimulant drugs affect mood and alertness, and depress food appetite by increasing levels of several neurotransmitters in the brain. Although the exact therapeutic mode of action of methylphenidate is not known, the drug has been shown to elevate levels of some of these neurotransmitters, primarily dopamine and norepinephrine (noradrenaline).

Dopamine and norepinephrine are excitatory neurotransmitters. When nerve cells in the brain are stimulated, neurotransmitters stored in vesicles in nerve cell endings are released to extracellular spaces (synapses). The liberated chemical messengers can then interact with receptors on an adjacent nerve cell and can generate a new nerve signal (a nerve impulse). When levels of dopamine or norepinephrine are depressed, regions of the brain that rely on the two substances to regulate nerve impulse conduction are unable to function properly. Research has shown that children with ADD or ADHD have lower levels of dopamine in the CNS. It is believed that drugs acting as CNS stimulants, such as amphetamine, cocaine, and methylphenidate, compensate for lowered levels of excitatory neurotransmitters (i.e., dopamine and norepinephrine) in the brain. Indeed, administration of methylphenidate to healthy adult men has been found to increase dopamine levels.

Different theories have been proposed to explain how methylphenidate increases levels of dopamine in the brain. One such theory propounds that methylphenidate causes dopamine to remain longer in extracellular spaces. Once a neurotransmitter has transmitted its message, it dissociates from the receptor to which it was bound and is taken up by the nerve cell from which it was originally released. Researchers at Brookhaven National Laboratory have demonstrated that methylphenidate inhibits this "reuptake" of dopamine by nerve cells. As a result, extracellular dopamine levels are increased, and the neurotransmitter continues to be available to initiate nerve impulses.

Ritalin is the brand name of a formulation of methylphenidate that is available in tablet form. Ritalin tablets are most often prescribed to children, aged 7 to 18, who have been diagnosed with ADHD. However, individuals who suffer from anxiety or panic disorders are warned not to take the drug, as Ritalin may aggravate symptoms of agitation and/or anxiety. Nervousness and insomnia are the most common side effects associated with Ritalin. There have also been reports of the onset of Tourette's syndrome, a neurological disorder characterized by repeated and involuntary body movements (tics), or at least of symptoms resembling those of Tourette's, in patients taking Ritalin, and therefore patients with this disorder are advised not to take Ritalin. In April 2002 the National Institutes of Health reported that a combination of Ritalin and Clonidine, a drug often used to treat hypertension , is more effective in the treatment of ADHD than either drug alone. Furthermore, Clonidine is reported to have a tic-suppressing effect, and it is believed that the drug may counteract the apparent tic-accentuating effect of methylphenidate.

During the early 1990s, reports of abuse of methylphenidate began to appear. Nonmedical use of the drug for its stimulant effects impelled the U.S. Drug Enforcement Administration (DEA) to regulate the manufacture, distribution, and prescription of methylphenidate. Because methylphenidate is related to amphetamine, it can be addictive and result in physical and psychological dependence.

SEE ALSO Neurochemistry ; Neurotransmitters ; Pharmaceutical Chemistry .

Nanette M. Wachter

Bibliography

Goldman, Larry S., et al. (1998) "Diagnosis and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents." Journal of the American Medical Association 279(14):1100–1107.

Internet Resources

National Institute of Drug Abuse. National Institutes of Health. Available from http://www.nida.nih.gov/ .

National Institute of Neurological Disorders and Stroke. Available from http://www.ninds.nih.gov/ .