Neurotransmitter interactions in schizophrenia—therapeutic implications

The search for new and improved antipsychotic agents has escalated during the past five years. The era of searching for non-toxic copies of clozapine has been followed by several different lines of research, some of which pursue the traditional dopamine track, although at a higher level of sophistication, whereas others focus on other neurotransmitters, such as serotonin and glutamate. Emerging knowledge about the interactions between different neurotransmitters in complex neurocircuits opens up possibilities for achieving antipsychotic activity by interfering with many different neurotransmitters. Most intriguing is the finding in animal experimental models, indicating that it should be possible to alleviate psychotic conditions by stabilizing rather than paralyzing neurocircuits, thus avoiding the risk of motor and mental side effects of the currently used drugs. Among these new classes dopaminergic stabilizers and 5-HT2A receptor antagonists seem to offer most promise at present. In a longer perspective, drugs interfering with glutamate function via different mechanisms may also turn out to be useful, especially in the control of negative symptoms.