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Recall from slide
#13 that antipsychotics were the top selling drugs in the United States in
2009 (14.6 billion dollars). The
history of antipsychotic drugs dates back to the early 1950s when physicians
in France hypothesized that sedating chemicals might be valuable in “taming”
the residents of the world’s asylums.
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There are two major
ways of describing the evolution of antipsychotic drugs. As shown above, it is possible to describe
this history in terms of “when” the
drugs entered clinical use. A second method refers to the molecular and
physiological effects of each agent.
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According to this
latter approach, the “first” generation drugs (typical or conventional
antipsychotics) are associated with the blockade of dopamine receptors and
specific kinds of adverse effects. The
so-called “second” generation drugs (atypical antipsychotics) are
distinguished by the blockade of dopamine and serotonin receptors, along with
an “allegedly” more benign side effect profile. The so-called “third generation” drugs
(such as Abilify) is characterized by its affinity for specific states of the
dopamine receptor (partial agonism).
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Unfortunately, the
myth of “atypicality” has not held up.
Many consumers of 2nd and 3rd generation drugs
have developed Parkinson’s disease, tardive dyskinesia, and diabetes. Astute clinicians have openly questioned
the classification of the newer products, such as Risperdal (risperidone),
after finding that recommended doses have induced toxicities identical to
those which are commonly inflicted by the older drugs.
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