Antipsychotic Timeline
•*timeline  = year that the drug was invented or first used
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•1st generation drugs 1950 to 1960s
• Thorazine, Haldol, *Clozaril
•2nd generation drugs 1970 to 1990s
• Risperdal, Zyprexa, Seroquel, Geodon
•3rd generation drugs 2000 to 2010
• Abilify
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•*Invented in 1958, clozapine was introduced in Europe in the early
•1960s.  It did not gain FDA approval in the U.S.A. until 1989.  Partly for this
•reason, American physicians refer to it as a “second generation” drug.
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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.

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.

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).

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.