Neurotransmitter interactions in schizophrenia-therapeutic implications

The search for new and improved antipsychotic agents has increased in inten sity 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 a s serotonin and glutamate. Emerging knowledge about the interactions betwee n different neurotransmitters in complex neurocircuits opens up possibiliti es for achieving antipsychotic activity by interfering with many different neurotransmitters. Most intriguing is the finding in animal experimental models, indicating th at it should be possible to alleviate psychotic conditions by stabilizing r ather than paralyzing neurocircuits, thus avoiding the risk of motor and me ntal side effects of the currently used drugs. Among these new classes, dop aminergic stabilizers and 5-HT2A receptor antagonists appear to offer the m ost promise at present. In a longer perspective, drugs interfering with glu tamate function via different mechanisms may also turn out to be useful, es pecially in the control of negative symptoms.