Many psychomotor stimulants
possess activities similar to those of amphetamine and have been discussed
pre-viously . Of primary importance to our discussion of the psychomotor
stimulants are ampheta-mine (Adderall, Benzedrine, Dexedrine),
methampheta-mine (Desoxyn), and
methylphenidate (Concerta, Ritalin, Metadate, Methylin).
All of these compounds are
well absorbed after oral administration, leaving injectable forms with few
legiti-mate applications. Although several catabolic pathways metabolize the
amphetamines, a considerable portion of untransformed drug is excreted in the
urine. Thus, it is possible to ion-trap this weak organic base by acidify-ing
the urine, thereby reducing its reabsorption in the renal tubules and enhancing
There is good evidence that
the facilitation of peripheral sympathetic nervous system transmission produced
by the amphetamines also occurs in the CNS. The possibility that amphetamines
act indirectly (i.e., by releasing monoamines) at monoaminergic synapses in the
brain and spinal cord seems likely. However, amphetamine has effects beyond
displacement of catecholamines; these in-clude inhibition of neuronal amine
uptake, direct stimula-tion of dopamine and serotonin receptors, antagonism of
catecholamine action at certain subtypes of adrenocep-tors, and inhibition of
monoamine oxidase. Interestingly, none of these actions explains the
therapeutic benefit of the amphetamines in hyperkinetic children.
The therapeutic indications
for the psychomotor stimu-lants are quite limited. They are beneficial in the
treat-ment of the hyperkinetic syndrome
(attention deficit– hyperactivity disorder with minimal brain dysfunction).
This is generally a childhood disease characterized by hyperactivity, inability
to concentrate, and impulsive be-havior. Amphetamines and the more extensively
used methylphenidate paradoxically are quite effective in calming a large
proportion of children with this disor-der. Pemoline (Cylert) is also used in the treatment of attention deficit disorder
with hyperkinetic behavior. The mechanism by which these compounds are
effec-tive in this disorder is not known.
Narcolepsy is another medically recognized indica-tion for the use of the
psychomotor stimulants. This dis-order is characterized by sleep attacks,
particularly dur-ing the day, sudden loss of muscle tone (cataplexy), sleep paralysis, and vivid visual and auditory
nightmares that may persist into the waking state. Drugs that influ-ence the
central action of adrenomimetic amines re- markably affect narcolepsy.
Monoamine oxidase in-hibitors (e.g., selegiline) and amphetamines are both
quite effective in preventing sleep attacks and improv-ing cataplexy. Modafinil
(Provigil) is a nonampheta-mine
compound whose mechanism of action is not known but that has been shown to be
successful in the treatment of narcolepsy. However, amphetamine and
methylphenidate are still considered among the drugs of choice in this
Previously, another use of
the amphetamines and other centrally acting adrenomimetics has been in the
management of obesity and weight reduction. Although the amphetamines have a
significant anorexic effect, tolerance to this action develops within a few weeks.
In addition, insomnia restricted their use during the latter part of the day.
The combined drawbacks of the devel-opment of tolerance and potential for drug
abuse have convinced much of the medical community that the use of amphetamines in
weight control is inappropriate.
Fenfluramine (Pondimin) and phentermine (Adipex-P, Fastin) are anorexigenic drugs
that produce depres-sion of the CNS
and at one time were used (Fen-phen) in
the treatment of obesity. Sibutramine (Meridia)
is also available for the treatment of obesity.
The acute effects of
psychomotor stimulant overdoses are related to their CNS stimulant properties
and may include euphoria, dizziness, tremor, irritability, and in-somnia. At
higher doses, convulsions and coma may en-sue. These drugs are cardiac
stimulants and may cause headache, palpitation, cardiac arrhythmias, anginal
pain, and either hypotension or hypertension. Dextro-amphetamine produces
somewhat less cardiac stimula-tion. Chronic intoxication, in addition to these
symp-toms, commonly results in weight loss and a psychotic reaction that is
often diagnosed as schizophrenia.
These agents produce
addiction, including psycholog-ical dependence, tolerance, and physical
dependence. Psychic dependence also has been seen following high doses of
methylphenidate.The abstinence syndrome seen after abrupt discontinuation of
amphetamines is neither as dramatic nor as predictable as that observed during
withdrawal from the barbiturates or opioids. With the amphetamines, the abstinence
syndrome consists prima-rily of prolonged sleep, fatigue, and extreme hunger (hy-perphagia). These symptoms may be
accompanied by profound and