Methylphenidate, commonly known as Ritalin, is a commonly prescribed central nervous system stimulant used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy. Medical use of methylphenidate began in 1960 and an estimated 2.4 billion doses are prescribed a year. Methylphenidate is thought to act through the inhibition of dopamine and norepinephrine transporters in neurons, especially those of dopaminergic pathways of the brain. The dopaminergic pathways of the brain are composed of neurons that synthesize and transmit the neurotransmitter dopamine, to different regions of the brain. Dopamine signaling from these pathways is associated with several integral cognitive processes including reward-motivated behavior, motor
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Physiologically methylphenidate acts like other central nervous system stimulants and produces several effects including increased alertness and increases in blood pressure, heart rate, respiration, and body temperature. It has also been found to increase regional cerebral blood flow in the midbrain/substantia nigra and thalamus. In small-scale studies in children with ADHD, methylphenidate modulates the activity and connectivity between ] frontal-striatal and frontal-parietal regions of the brain. These modulations suppress the activity in the default mode network, which is involved in mind-wandering. A recent meta-analysis of functional magnetic resonance imaging in patients with ADHD suggests that the long-term use of stimulants, like methylphenidate, may change the size of some brain structures that are typically smaller in children with ADHD …show more content…
When the drug was first introduced it was sold as a racemic mixture of the isomers, but today the drug is also sold as with only d-threo-methylphenidate. Studies have shown there were few differences in binding affinities between the isomers (Markowitz). However, studies using Positron Emission Tomography in the human brain with radioactively-labeled methylphenidate have shown that therapeutic doses block more than 50% of the dopamine transporters, and significantly enhance extracellular dopamine (DA) in the basal ganglia. Recent in-vitro studies have shown d-methylphenidate exhibits significant affinity with the norepinephrine transporter as well as the dopamine transporter when compared to l-methylphenidate (Hannestad). These studies have shown methylphenidate to be potent inhibitor of both the dopamine transporter and norepinephrine transporter with experimentally determined KIs of = 0.06 μM and 0.10 μM respectively. KI is an indicator of inhibitor potency and corresponds to the concentration required to produce half maximum
Physiologically methylphenidate acts like other central nervous system stimulants and produces several effects including increased alertness and increases in blood pressure, heart rate, respiration, and body temperature. It has also been found to increase regional cerebral blood flow in the midbrain/substantia nigra and thalamus. In small-scale studies in children with ADHD, methylphenidate modulates the activity and connectivity between ] frontal-striatal and frontal-parietal regions of the brain. These modulations suppress the activity in the default mode network, which is involved in mind-wandering. A recent meta-analysis of functional magnetic resonance imaging in patients with ADHD suggests that the long-term use of stimulants, like methylphenidate, may change the size of some brain structures that are typically smaller in children with ADHD …show more content…
When the drug was first introduced it was sold as a racemic mixture of the isomers, but today the drug is also sold as with only d-threo-methylphenidate. Studies have shown there were few differences in binding affinities between the isomers (Markowitz). However, studies using Positron Emission Tomography in the human brain with radioactively-labeled methylphenidate have shown that therapeutic doses block more than 50% of the dopamine transporters, and significantly enhance extracellular dopamine (DA) in the basal ganglia. Recent in-vitro studies have shown d-methylphenidate exhibits significant affinity with the norepinephrine transporter as well as the dopamine transporter when compared to l-methylphenidate (Hannestad). These studies have shown methylphenidate to be potent inhibitor of both the dopamine transporter and norepinephrine transporter with experimentally determined KIs of = 0.06 μM and 0.10 μM respectively. KI is an indicator of inhibitor potency and corresponds to the concentration required to produce half maximum