Recognizing that these agents, the neuroleptics, were all variably potent antagonists of dopamine receptors, the dopamine hypothesis of schizophrenia was promoted . Subsequent to the identification of dopamine receptor subtypes (now subclassified as D1 to D5), the dopamine theory was refined with the D2 receptor becoming the focus until more recently. D2 receptor blockade in the limbic system of the brain is believed to be associated with effect on positive symptoms. The major drawbacks of these conventional agents, extrapy-ramidal side effects (EPS), tardive dyskinesias (TD) and hyperprolactinemia, also result from D2 blockade, but in regions distinct from the limbic system. Such drug-induced abnormal movements can significantly limit the acceptability of these medications. In addition, approximately 30% to 50% of patients do not respond or are only partially responsive to conventional agents with negative and cognitive symptoms often persisting. buy prednisone
The development of second generation antipsychotics came about with the reintroduction of clozapine in the early 1980s. Clozapine revealed similar efficacy to haloperidol with less propensity to induce EPS, although exhibiting a dissimilar receptor binding profile. The pathophysiology of schizophrenia was recognized to be more complex than an overactivity of the dopamine system and appeared to involve other neurotransmitter interactions.