How Effective are Dopamine D2 Partial Agonists as Antipsychotics?
Although one D2 partial agonist (aripiprazole) is approved as an antipsychotic, all other proven antipsychotics are D2 antagonists or inverse agonists.1 Clinical experience with DPAs1,4-7 suggests that only those close to the antagonist end of the spectrum may have antipsychotic efficacy, and the closer the partial agonist is to the full agonist end of the spectrum, the less effective it becomes as an antipsychotic, the more difficult it is to find the optimal dose, and the more activating and psychotomimetic it becomes (Figure).1 For example, the partial agonist OPC 4293 was developed in the same laboratory as aripiprazole, but was found to be too activating, improving negative symptoms of schizophrenia but worsening positive symptoms. It was “too full” of a partial agonist (Figure).1 In response, a “less full” partial agonist, OPC 14597, now known as aripiprazole, was tested in schizophrenia and found to be an effective antipsychotic.1-5 Actions at serotonin receptors may also contri
