Molecular attributes of dopamine receptors: new potential for antipsychotic drug development

The neurotransmitter dopamine (DA) plays a central role in the control of motor function, emotional states, and endocrine physiology. The discovery that schizophrenic symptoms can be alleviated by neuroleptic drugs and the finding that these drugs interact at dopamine receptors has indicated involvement of the dopamine system in schizophrenia. The dopamine system has recently been shown to rely on the activation of five distinct subtypes of DA receptors (D1-D5) identified by molecular cloning, and pharmacological studies have specifically implicated the D2-like receptors (D2R, D3R and D4R) in antipsychotic action. In addition, the localization of D3R and D4R expression in the mesolimbic/mesocortical DA pathways is consistent with their proposed involvement in affective behaviour, and suggests that drugs developed specifically for these receptor subtypes might have potent antipsychotic activity with a lower propensity for extrapyramidal, endocrine, and cognitive side-effects.