Dopamine and Dopamine-Related Ligands Can Bind Not Only to Dopamine Receptors

The dopaminergic system is one of the most important neurotransmitter systems in the central nervous system (CNS). It acts mainly by activation of the D-1-like receptor family at the target cell. Additionally, fine-tuning of the signal is achieved via pre-synaptic modulation by the D-2-like receptor family. Some dopamine drugs (both agonists and antagonists) bind in addition to DRs also to alpha(2)-ARs and 5-HT receptors. Unfortunately, these compounds are often considered subtype(s) specific. Thus, it is important to consider the presence of these receptor subtypes in specific CNS areas as the function virtually elicited by one receptor type could be an effect of other-or the co-effect of multiple receptors. However, there are enough molecules with adequate specificity. In this review, we want to give an overview of the most common off-targets for established dopamine receptor ligands. To give an overall picture, we included a discussion on subtype selectivity. Molecules used as antipsychotic drugs are reviewed too. Therefore, we will summarize reported affinities and give an outline of molecules sufficiently specific for one or more subtypes (i.e., for subfamily), the presence of DR, alpha(2)-ARs, and 5-HT receptors in CNS areas, which could help avoid ambiguous results.

Automated summary

The dopaminergic system is crucial in the central nervous system, acting through different receptor families to transmit signals. Some dopamine drugs may also bind to other receptors, highlighting the importance of understanding the presence and effects of these receptors to avoid ambiguous results.