Dopamine Receptor Pharmacology: Interactions with Serotonin Receptors and Significance for the Aetiology and Treatment of Schizophrenia

Abstract

The classification of dopamine receptors proposed more than two decades ago remains valid today. Based on biochemical and pharmaceutical properties two main classes of dopamine receptors can be distinguished: D(1)-like (D(1), D(5)) and D(2)-like (D(2), D(3), and D(4)) dopamine receptors. Dopamine receptors belong to the class of G protein-coupled receptors and signal to a wide range of membrane bound and intracellular effectors such as ion channels, secondary messenger systems and enzymes. Although the pharmacological properties of ligands for D(1)-like and D(2)-like dopamine receptors are quite different, the number of selective ligands for each of the five receptors subtypes is rather small. Many drugs used to treat neurological and neuropsychiatric disorders like Parkinson's disease, restless leg syndrome and schizophrenia have affinities for dopamine receptors. Such medications are not without limitations so the development of novel (selective or aselective) dopamine receptor ligands is of the utmost importance for improved therapeutic approaches for these diseases. In that respect it is also important to understand how dopamine receptor ligands affect receptor signalling processes such as desensitization, receptor heterodimerization and agonist-receptor trafficking, issues which will be discussed in the present review. Furthermore, attention is paid to interactions of dopamine receptors with serotonin receptors since many drugs used to treat above mentioned disorders of the brain also possess affinities for serotonin receptors. Because of the enormity of this area we have tried to focus more specifically on interactions within the prefrontal cortex where it appears that the serotonergic modulation of dopaminergic function might be very relevant to schizophrenia.

Behavioral economics of food reinforcement and the effects of prefeeding, extinction, and eticlopride in dopamine D2 receptor mutant mice

“…One difference between the current study and those indicating equivalent effects of extinction and effects of DA antagonists is the drug used (eticlopride vs, pimozide). As eticlopride and pimozide are both relatively selective for DA D 2 Rs (Christensen et al 1984; Werkman et al 2006), the different drugs employed seems an unlikely source for the different outcomes.…”

Pharmacological Modulation of Nrf2/HO-1 Signaling Pathway as a Therapeutic Target of Parkinson’s Disease

“…DA eventually degrades to homovanillic acid (HVA) under the action of monoamine oxidase-B (MAO-B) and catechol-o-methyltransferase (COMT), producing H 2 O 2 ( Zhang S. et al, 2019 ). Once the excitation of DAergic neurons, dopamine in synaptic vesicles is released into the synaptic cleft from dopaminergic axon terminals and then binds to its receptors that are localized in postsynaptic dendrites/neurons ( Werkman et al, 2006 ; Zhang B. et al, 2019 ). At a later stage, the excitation signal is terminated and the extracellular free DA is removed from the synaptic cleft by the dopamine transporter (DAT) expressed on the dopaminergic nerve endings and can be reutilized by DAergic neurons or taken up by astrocytes.…”

Class A and C GPCR Dimers in Neurodegenerative Diseases

“…Different studies located the 5-HT 1A R-DRD 2 in the dorsal and ventral striatum using in situ PLA and FRET as well as in cellular models using BRET [ 662 - 664 ]. The 5-HT 1A R-DRD 2 has been developed as an important therapeutic target due to a well-documented serotonin-dopamine interaction and its relevance to schizophrenia [ 665 ].…”