Sixty-year history of dopaminergic mechanism of antipsychotic drugs

Objective.
Sixty-year history of the role of the dopaminergic system in the antipsychotic drugs’ action.

Literature review.
Sixty years ago, an article suggested the role of the dopaminergic system in the mechanism of action of neuroleptic (antipsychotic) drugs. The author was Arvid Carlsson who in 2000 was awarded the Nobel Prize for his research on the pathogenic and therapeutic role of dopamine. A portrait of this researcher was sketched. Next, the development of the dopaminergic theory of antipsychotic drugs was presented. A concept of dopaminergic receptor blockade was depicted and the dopaminergic D₂ receptors were identified as a main element of antipsychotic drug action. A novel finding was the discovery of partial agonists of D₂ receptors. The effect on the dopaminergic system and interactions with other neurotransmitters have formed the basis for the identification of three generations of antipsychotic drugs. The first generation of antipsychotics was characterised by the blockade of dopaminergic D₂ receptors and the second generation additionally by the blockade of serotonergic 5-HT₂ receptors. The third generation includes drugs characterised by partial agonism for D₂ receptors and those acting on dopaminergic D₃ receptors and serotonergic receptors 5-HT_1A and 5-HT₇. These groups differ as to the therapeutic spectrum, covering various domains of schizophrenia as well as other psychiatric disturbances, mainly bipolar mood disorder.

Conclusions.
The effect on the dopaminergic system is the main therapeutic mechanism of antipsychotic drugs. Suggestions of a possible antipsychotic effect due to a predominant influence on other neurotransmitter systems (glutamatergic, serotonergic, cholinergic) have not been sufficiently confirmed.