John A. Lowe* Pages 50 - 60 ( 11 )
Medicinal chemistry has played a major role in the improvement of antipsychotic therapy by helping to develop the D2/S-HT2ratio hypothesis. Early pharmacological insights implicating a role for serotonin in schizophrenia by virtue of its control of the dopamine system have been tested by numerous combined D2/S-HT2 receptor antagonists. Recent work indicates that 5-HT2 receptor blockade can compensate for relatively weaker D2 receptor affinity, lessening the chance of side effects while maintaining antipsychotic efficacy. Many of the newer agents are poised to test the validity of the D2/S-HT2 ratio hypothesis in the clinic.