The “classic” antipsychotic drugs fail to reduce negative and cognitive symptoms
ID: 130748 • Letter: T
Question
The “classic” antipsychotic drugs fail to reduce negative and cognitive symptoms of schizophrenia. The newer atypical antipsychotic drugs can reduce all three categories of schizophrenic symptoms; positive, negative and cognitive. How do these atypical antipsychotics work? Using the “third generation” antipsychotic drug, Aripiprazole, as your atypical antipsychotic drug, explain how it works, according to the Carlson text. Consider that Aripiprazole is a partial agonist at dopamine receptors. Is that important information in understanding the mechanisms of how it works as an antipsychotic drug? Please review Figure 15.7 in your text and use that information in your Discussion answer. Please read the text material relevant to Figure 15.7 before you formulate your answer.
398 CHAPTER 1S: Schizophrenia, Affective Disorders, and Anxiety Disorders The research findings presented in this subsection explain why the "classic" antipsychotic drugs fail to reduce negative and cognitive symptoms: One of the causes of these symptoms is decreased activation of dopamine receptors in the prefrontal cortex, and drugs that block dopamine receptors would, if anything. make these symptoms worse. What is different about the newer atypical antipsy chotic drugs that enables them to reduce all three categories of schizophrenic Partial agonst diaplaoes symptoms? The atypical antipsychotic drugs seem to do the impossible: They increase dopaminergic activity in the prefrontal cortex and reduce it in the mesolimbic system, Let's examine the action of a so-called "third generation" antipsychotic drug, aripiprazole (Winans, 2003; Lieberman, 2004). Aripiprazole acts as a partial agonist at dopamine receptors. A partial agonist is a drug that has a very high affinity for a particular receptor but activates that receptor less than the normal ligand does. This means that in a patient with schizophrenia, aripiprazole serves as an antagonist in the mesolimbic system, where too much dopamine is pres- ent, but serves as an agonist in regions such as the prefrontal cortex, where too little dopamine is present. Hence, this action appears to account for the abil ity of aripiprazole to reduce three categories of schizophrenic symptoms. 1.0 101.0 10 10 05 0.5 10 05 05 Paräal agonist binde wth Mean opening FIGURE 15.7 Effects of a Partial Agonist. The diagram explains the differential effects of a partial agonist in regions of high and low concentrations of the normal ligand. Numbers beneath each receptor Schizophrenia is a puzzling and serious disorder, which has stimulated many ingenious hypotheses and much research. Some hypotheses have been proved wrong: 0-fully open, o.s partially open,0.0-fully closed. others have not yet been adequately tested. Possibly, future research will find that all of these hypotheses (including the ones I have discussed) are incorrect or that one the extracellular concentration of the neurotransmitterthat I have not mentioned is correct. However, I am impressed with recent research, is high and increase it when the extracellular concentration of the neurotransmitter is low and I believe that we have real hope of finding the causes of schizophrenia in the near future. With the discovery of the causes we can hope for the discovery of methods of partial agonist A drug that has a very high affinity for a partikcular receptor but activates that receptor less than the normal ligand does: serves as an agonist in regions of low concentration of the normal ligand and as an antagonist in regions of high concentrations. prevention and not just treatment.Explanation / Answer
Consider that Aripiprazole is a partial agonist at dopamine receptors. Is that important information in understanding the mechanisms of how it works as an antipsychotic drug?
Yes, this information is important as it forms the basis in which aripiprazole would bind in the presence and absence of dopamine, which defines its actions.
Using the “third generation” antipsychotic drug, Aripiprazole, as your atypical antipsychotic drug, explain how it works, according to the Carlson text?
The dopaminergic activity in the prefrontal cortex is increased with a reduction in the mesolimbic system. Aripiprazole is not a complete agonist but a partial agonist that would be having very high affinity for one particular receptor but activation of the receptor is not complete, but less than normal activation. Aripiprazole would act as an antagonist of the mesolimbic system if there is presence of too much dopamine, but at places where dopamine is less, the prefrontal cortex, it would serve as an agonist. As a result, aripiprazole would reduce all three categories of symptoms as seen in schizophrenia.
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