Dr. Carlsson pointed out that chlorpromazine greatly improved the behavior of chronically psychotic patients when it was first introduced in the 1950s. At the time there was no sound theory about the mechanism of action of this drug. All of the theories about mechanisms of action in the brain involved electric currents only and not chemical effects.

Bernard Brodie at the National Heart Institute developed a way to measure serotonin, which led to an experiment in which researchers gave reserpine to animals and then measured their serotonin levels. It was found that serotonin was completely depleted after reserpine was given.

Dr. Ake-Nils Hillarp developed a method to study catecholamines. Dr. Carlsson joined him, and together they began to study the effects of reserpine on catecholamines. They discovered reserpine also diminishes catecholamines. However, L-dopa reverses the effects of reserpine in animals without changing the noradrenaline levels. Thus, after a series of experiments, in 1958 the first relation between reserpine's action and dopamine was discovered. This was the first time that a drug's effects on behavior were related to chemicals in the brain. The world experts in chemical transmission in the peripheral nervous system rejected this idea at the time.

With the help of experiments using new immunofluorescence techniques, Dr. Carlsson suggested that chlorpromazine affects receptors in the brain. This was the birth of "the dopamine hypothesis" of schizophrenia, in 1965. It also marked the beginning of the neurotransmitter era.

Many effective neuroleptic medications have been developed based on the dopamine hypothesis and the neurotransmitter paradigm. The exploration of medications with fewer side effects has led to the investigation of other neurotransmitter systems and the development of the atypical antipsychotics.

For the future, Dr. Carlsson suggests that partial dopamine agonists will emerge as treatments. These drugs offer more selective dopamine effects. Antagonism is especially prominent in brains that have an excess of dopamine. At the same time, these drugs have fewer effects on the normal brain. This may provide greater therapeutic effects with fewer side effects.

Dr. Carlsson also feels optimistic about the idea of examining the glutamatergic system as part of the search for effective new drugs for schizophrenia.