Neurotransmitter interactions in schizophrenia - Therarpeutic implications

The search for new and improved antipsychotic agents has escalated during t he 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 pur sue the traditional dopamine track, although at a higher level of sophistic ation, whereas others focus on other neurotransmitters, such as serotonin a nd glutamate. Emerging knowledge about the interactions between different n eurotransmitters in complex neurocircuits opens up possibilities for achiev ing antipsychotic activity by interfering with many different neurotransmit ters. Most intriguing is the finding in animal experimental models, indicat ing that it should be possible to alleviate psychotic conditions by stabili zing rather than paralyzing neurocircuits, thus avoiding the risk of motor and mental side effects of the currently used drugs. Among these new classe s dopaminergic stabilizers and 5-HT2A receptor antagonists seem to offer mo st promise at present. In a longer perspective, drugs interfering with glut amate function via different mechanisms may also turn out to be useful, esp ecially in the control of negative symptoms. Biol Psychiatry 1999; 46:1388- 1395 (C) 1999 Society of Biological Psychiatry.