Sympathomimetic Agents Psychomotor Stimulants

Sympathomimetic agents, whose effects are manifested mainly in the periphery, are discussed in Chapter 16. A few simple structural changes in these peripheral agents produce compounds that are more resistant to metabolism, more nonpolar. and better able to cross the blood-brain barrier. These effecLs increa.se the ratio of central to peripheral activity, and the agents are designated, somewhat arbitrarily, as central sympathomimetic agents. 

Structural features for many of the agents can be visualized easily by considering that within their structure they 

TABLE 15-3 Sympathomimetics With Significant Central Stimilant Activity 

Methoxyl or methyicnedioxy substitution on the rinc tends to produce psychotomimetic agenl.s. suggesting ho-pism for dopaminergic (D2) receptors. 

N-methylation increases activity (c.g.. compare mcthaiti-phetaminc with dextroamphetamine). Di-N-mcthylation decreases activity. Mono-N substituents larger than methyl tk-crease excitatory properties, but many compounds reiaio anorexiant propettie.s. Consequently, some of these ageoK arc used as anorexiants, reportedly with less abuse poteniial than amphetamine. 

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B. Psychomotor stimulants such as amphetamine are also indirectly acting sympathomimetics that increase the release of catecholamines from sympathetic nerve terminals. While amphetamine and other congeners possess additional actions on peripheral sympathetic nerves, this is the most likely explanation for the cardiac stimulation observed following the administration of these agents. 

Dexamphetamine is one of the most powerful and best known psychomotor stimulants, and other similar agents include dexfenfluramine. diethylpropion and fenfluramine. All these are on the controlled drugs list, and have a limited medical use as appetite suppressants. Such drugs work by interacting with the release of monoamines within the central (and peripheral) nervous system, and can be regarded as indirect SYMPATHOMIMEtics. Recently, there has been some use of the weak amphetamine-like stimulant methylphenidate to treat attention-deficient hyperactivity disorder (ADHD) in children. 

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