Antipsychotic drugs serotonin-dopamine antagonists

Consistent with the role of both serotonin and dopamine in OCD, some OCD patients benefit from treatment with the new serotonin-dopamine antagonists (also known as atypical antipsychotics), especially when there is inadequate response to an SSRI. On the other hand, other patients have no therapeutic response to these new agents, and the condition of still others is even worsened by these drugs. The atypical antipsychotics and serotonin dopamine antagonism are discussed in Chapter 11. 

FIGURE 11-23. Here postsynaptic dopamine 2 receptors are being blocked by a serotonin-dopamine antagonist (SDA) atypical antipsychotic in the nigrostriatal dopamine pathway. This shows what would happen if only the dopamine 2 blocking action of an atypical antipsychotic were active— namely, the drug would only bind to postsynaptic D2 receptors and block them. However, see Figure 11-24. 

Which of the following serotonin dopamine antagonists (SDAs) is not considered to be a first line atypical antipsychotic drug ... 

No recognised classification system exists for atypical antipsychotics.Tentative terms based on receptor binding profiles have been applied to certain drug groupings.for example broad spectrum atypicals for clozapine, olanzapine and quetiapine. whilst risperidone and ziprasidone have been described as high affinity serotonin-dopamine antagonists . 

The large majority of antipsychotic drugs act mainly as dopamine receptor antagonists reducing the excess responsiveness to that neurotransmitter present in psychoses. It was found a decade ago that antagonists of serotonin H2 showed promising antipsychotic activity in several model systems. These dmgs would be better tolerated than their predecessor since they should be devoid of side effects... 

It is believed that although antipsychotic medications block norepinephrine, serotonin, and acetylcholine, their primary action is as central dopamine antagonists (Galenberg, 1991 Meyer Quenzer, 2005). That is, these drugs block central dopamine receptors, particularly the Dj subtype, and thus inhibit dopaminergic neurotransmission in the brain. The postsynaptic receptor blockade in the limbic system is thought to reduce the schizophrenic symptoms. 

Many of the side effects associated with antipsychotic agents can be attributed to their antagonist activity at a variety of CNS receptors, which include histamine Hi, adrenergic 01/02, cholinergic Mi receptors, serotonin 5-HT2, and dopamine D2 receptors in the brain. For example, antipsychotic drug side effects such as sedation. 

Iloperidone is a novel antipsychotic drug which is a mixed dopamine D2/serotonin 5-HT2A receptor antagonist. In 2008, the US Food and Drug Administration required Vanda Pharmaceuticals, the manufacturers, to carry out a comparison of iloperidone with placebo and an active comparator such as olanzapine or risperidone [80 ]. It was finally approved in the USA in May 2009. 

The dopamine hypothesis of schizophrenia posits that such symptoms arise because of a functional excess of dopaminergic activity in the CNS. The notion is based on the facts that drugs that activate DA receptors may cause psychotic symptoms and those that block DA receptors often have antipsychotic actions. However, drugs used for schizophrenia do not remedy all symptoms they are not curative, and some newer agents appear to be effective in many patients, even though they do NOT act as antagonists at brain DA receptors but may modify serotonin functions. 

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