Attention-deficit/hyperactivity disorder structural

L. J. Seidman, E. M. Valera and N. Makris, Structural brain imaging of attention-deficit/ hyperactivity disorder. Biol Psychiatry, 2005, 57,1263-1272. 

One of the most controversial CNS-acting drugs in contemporary society is methylphenidate (Ritalin ). This drug is structurally related to amphetamine and is a mild stimulant that has abuse potential similar to amphetamine. Methylphenidate is classified as a Schedule II controlled substance. It is effective in the treatment of narcolepsy and attention-deficit hyperactivity disorder (ADHD). Its use in ADHD has caused the greatest controversy. 

PS,PS)-2-Phenyl-2-(piperidin-2-yl)acetic acid methyl ester (INN methyl-phenidate) is a centrally acting sympathomimetic used in the treatment of attention-deficit/hyperactivity disorder in children. Dexmethylphenidate is the pure (and significantly more active) enantiomer with the R,R configuration available in the USA. The diastereomeric racemate with the RS,SR configuration whilst a commercially available chemical is not used as a pharmaceutical. (Note the small structural difference between these compounds and levofacetoperane, question 149). 

Methylphenidate (trade name Ritalin) is prescribed for attention deficit hyperactivity disorder (ADHD). Ritalin is a mixture of R,R and S,S isomers, even though only the R,R isomer is active in treating ADHD. (The single R,R enantiomer, called dexmethylphenidate, is now sold under the trade name Focalin.) Draw the structure of the R,R and S,S isomers of methylphenidate. 

Structurally-related drugs include dexamfet-amine (used for narcolepsy and in attention deficit hyperactivity disorder (ADHD) see p. 387), methylphenidate (used for ADHD), tenamfetamine (Ecstasy, see p. 189), phentermine, diethylpropion, and pemoline. 

Pemoline (cyleri, others), structurally dissimilar to methylphenidate, elicits similar changes in CNS function with minimal effects on the cardiovascular system. It is a schedule IV-controlled substance in the U.S. and is used in treating attention-deficit/hyperactivity disorder. It can be given once daily because of its long t. Clinical improvement may require treatment for 3 weeks. Pemoline has been associated with severe hepatic failure. 

Methylphenidate (Ritalin) is a behavioural stimulant used for the treatment of narcolepsy and attention deficit hyperactivity disorder (ADHD). It is commonly classified as a non-amfetamine but its nucleus is still present in that structure. The erytliro-racemate, i.e. (2 R,2"S)- and (2 S,2"R)-methylphenidate, shows negligible stimulant activity and is not used. The racemic threo-mcemate is responsible for activity but the (2 R,2"R)-enantiomer (dexmethylphenidate) displayed a more powerful inhibition of catecholamine uptake. 

Analysis of structured psychiatric interviews makes it possible to identify different subtypes of the disorder, depending on the prevalence (and persistence for at least 6 months) of different symptoms (9 for the attention deficit variant and 9 for the hyperactive variant) (i) ADHD, combined type subtype (6/9 or more inattention symptoms and 6/9 or more hyperactivity/impulsiv-ity symptoms) (ii) ADHD, predominantly inattentive type subtype (6/9 or more inattention symptoms, but fewer than 6/9 hyperactivity/impulsivity symptoms) (iii) ADHD, predominantly hyperactive-impulsive type sub-type (6/9 or more hyperactivity-impulsivity symptoms, but fewer than 6/9 inattention symptoms). The minimum score for a child to be considered to be affected with ADHD is therefore 6/9 for both ADHD, predominantly inattentive type and ADHD, predominantly hyperactive-impulsive type subtypes, and at least 12/18 for the ADHD, combined type subtype. 

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