Molecular biology of dopaminergic receptors: Pharmacological implications

Molecular biology techniques have had a tremendous impact on the studies of neurotransmitter receptors, in particular of dopamine receptors. Until recently only two dopamine receptors were described on the basis of pharmacological and biochemical experiments: the D1 and D2 receptors, differently coupled to adenyl cyclase and other second messenger systems. Molecular cloning studies have revealed the existence of five functional dopamine receptors. Several studies have been conducted regarding the distribution of these different receptor mRNAs and the expression of dopamine receptors in transfected cell lines in order to better understand the functional significance of the individual receptors. At present, little is known about the physiological and pharmacological importance of this receptor heterogeneity. Future reseach should allow us to get a better insight in the physical structure of these receptors in order to prepare highly selective dopaminergic ligands to use in the therapies related to dysfunction of the dopaminergic system. In fact this heterogeneity gives the possibility for developing selective antagonists for use in clinical therapeutics. Recently clinical studies have been focused on drugs like clozapine and risperidone which can modulate not only dopamine receptors but also serotonergic receptors (5HT2) having less extrapyramidal side effects characteristic of the blockage of D2 receptors.