Pharmacological Properties

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Several newspapers in the US recently reported the contention that healthy people should have the right to boost their brains with psychoactive drugs, drugs that are normally described for disorders such as attention deficit disorder (ADD), ► attention deficit/hyperactivity disorder (ADHD), ► narcolepsy, and memory-impairment in older individuals (► dementia). College students are already taking Ritalin as a ► cognitive enhancer before exams to help them study better, and some students contend that "We should welcome new methods of improving our brain function'' and that doing it with pills is no more morally objectionable than eating right or getting a good night sleep (Houston Chronicle, December 8, 2008). But what do we know about this psychoactive drug?

Psychoactive drug use is a practice that dates back to prehistoric times. A psychoactive drug is a central nervous system (CNS) stimulant that modulates consciousness, perception, mood, and behavior. There is archeological evidence of the use of psychoactive drugs as far back as several thousand years ago. These drugs were used thera-peutically as medication, for ritual and spiritual purposes, as well as recreationally to alter one's mood and to get "high." Because psychoactive drugs elicit changes in consciousness and mood, the user feels alert, joyful, pleasant, and becomes euphoric. Many psychoactive drugs are abused despite the risks of negative consequences, that is, ► dependence. Methylphenidate belongs to this family of drugs.

What is methylphenidate? MPD is one of the most prescribed psychostimulants for the treatment of children and adults with ADHD. ADHD is characterized by a persistent pattern of inattention and/or hyperactivity, with impulsivity more often displayed and more severe than is typical for individuals at a comparable level of development. ADHD is a developmental disorder that affects as much as 5-15% of school-aged children in the US (Kollins et al. 2001). Methylphenidate is a CNS stimulant that is structurally closely related to ► amphetamine. The neuropharmacological profile of methylphenidate is also similar to that of ► cocaine (Volkow et al. 1999). The drug was first synthesized in 1944 and was used initially as an analeptic for several types of barbiturate-induced coma. It was later used as a drug to improve memory in elderly patients. Since then, its usage has been extended to improve alertness and attention in children and adults with emotional, behavioral, and learning difficulties. Methylphenidate is highly effective in treating ADHD. Methylphenidate may also be useful in providing relief from intractable pain in narcolepsy and chronic fatigue. When methylphenidate is given orally, it is absorbed from the intestinal tract and has a half-life time of about 1 h with equally short duration and efficacy (Solanto 2000). Its peak level following injection (systemic) is faster and is reached in 8-20 min post injection (Kuczenski and Segal 1997), a pattern that is similar to systemic cocaine and amphetamine administration (Volkow et al. 1999). When methylphenidate is given systematically, it binds with similar affinity to the ► dopamine transporter (DAT) and has a potency (K;=200) similar to cocaine (K;=224) (Kuczenski and Segal 1997). The relationship between drug doses (milligrams of hydrochloride salt/kilogram of body weight) and percentage occupancy of DAT is identical for cocaine and methylphenidate in rodents and humans (Gatley et al. 1999). The dose and route of administration are important because the features of the behavioral and neurochemical responses to the drug are dependent on the speed of the drug to reach the peak level, that is, the rise time of drug concentration (Kuczenski and Segal 1997). Peak levels of methylphenidate following intravenous (i.v.), intraperitoneal (i.p.), and oral administrations were 8-20 min, 15-28 min, and 60-90 min, respectively (Gerasimov et al. 2000). Similar peak levels of i.v., i.p., and oral administrations were obtained following amphetamine and cocaine (Gerasimov et al. 2000). The ability to reach the peak level in a short time (i.v., 8-30 min) is one of the main

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