Evidence for the dopamine hypothesis of schizophrenia comes, in part, from the mechanism of action of known antipsychotic drugs. The therapeutic actions of typical antipsychotic drugs are due to blockade (antagonism) of D2 receptors, specifically in the mesolimbic dopamine pathway.[Stahl, 2013] This has the effect of reducing the excess release of dopamine in this pathway that is thought to cause the positive symptoms of psychosis.[Stahl, 2013] However, typical antipsychotics block D2 receptors throughout the brain and not just those in the mesolimbic dopamine pathway; this extensive blockade of D2 receptors is responsible for many undesirable adverse effects because it further reduces the already reduced dopamine levels in the mesocortical pathway.[Stahl, 2013]
Atypical antipsychotics, or second-generation antipsychotics, are more discriminating. Partial agonism of dopamine receptors results in stabilisation of dopamine neurotransmission in a state between fully on and fully off.[Stahl, 2013; Lieberman, 2004] Partial agonism is a neat answer to the conundrum of treating both a deficit of dopamine and dopamine overactivity in different areas of the brain.[Stahl, 2013; Lieberman, 2004]
References:
Stahl SM. Stahl’s Essential Psychopharmacology. Neuroscientific Basis and Practical Applications. Fourth Edition. © Cambridge University Press, 2013.
Lieberman JA. Dopamine partial agonists a new class of antipsychotic. CNS Drugs 2004; 18 (4): 251–267.