Side Effects of Dopamine-Blocking Medications

The predominant mechanism by which currently available antipsychotic medications interfere with dopamine activity is by blockade of dopamine receptors on neurons innervated by dopamine nerve terminals. Of the five types of dopamine receptors, all antipsychotics share in common the fact that they block the dopamine type 2 receptor, also known as the D2 receptor, to a varying degree. Some of the atypical antipsychotics also block other dopamine receptors (see Table 13.5). The role of blockade of Dl, D3, D4, and other dopamine receptors in the therapentic effects of antipsychotic drugs remains unclear. Aripiprazole is an exception to this in that it is a partial agonist at the D2 receptor. 

TABLE 13.5. Medications that Reduce Dopamine (DA) Activity 

Antidepressants that increase serotonin activity can also indirectly decrease dopamine activity by inhibiting the activity of dopamine-secreting nerve cells. This effect on dopamine nerve cells is generally not of sufficient magnitude to treat psychosis, but it may explain why patients taking these antidepressants on rare occasions experience akathisia and other extrapyramidal side effects. 

The Four Dopamine Pathways. There are four major dopamine circuits in the mammalian brain. They are known as the mesolimbic, mesocortical, tuberoinfun-dibnlar, and nigroneostriatal pathways. The mesolimbic pathway arises in the midbrain and projects to the so-called limbic structures. The mesocortical pathway arises in the midbrain and projects to frontal and temporal areas of the brain s cerebral cortex. 

Live to acetylcholine activity. When this happens, the classic symptoms of Parkinson s disease emerge inclnding a tremor, stiffness and rigidity, a stooped posture, a masklike expressionless face, and a slow shuffling gait. 

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