Neuroleptics serotonin receptor antagonists

As first choice treatment a well-established antihistamine such as meclozine is recommended. Promethazine is another antihistamine which reduces nausea, but sedation is a not always desired adverse effect. Metoclopramide increases intestinal motility and could be used short term also early in pregnancy. A neuroleptic such as prochlorperazine reduces nausea but should only be used for shortterm treatment due to the risk of extrapyramidal adverse reactions. Serotonin receptor antagonists can be used in post-operahve nausea and during treatment with cytostatics. 

The mechanism of action of neuroleptics is not sufficiently clear. However, it is believed that they are antagonists of dopamine and dopaminomimetics, and that their effect is connected in some way with the blockage of dopamine D receptors, which results in changes of behavioral reactions. Moreover, it is possible that they also block action on the serotonin receptors and M-choline receptors. It also is possible that antipsychotic agents disrupt the process of the release and return neuronal uptake of a number of biogenic amines. 

Figure 2.25 The atypical neuroleptic olanzapine 94 is a highly promiscuous ligand of many different G protein-coupled receptors (Table 2.1). The antidepressant mianserin 95 also is a promiscuous ligand in addition to its op-blocking activity, it blocks serotonin uptake and is a histamine, 5-HT2, and 5-HT3 antagonist.

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