ABSTRACT
G protein-coupled receptors (GPCRs) are the largest group of membrane receptors in the central nervous system and one of the key proteins for signal transduction between cells. Currently, many drugs available on the market act via GPCRs and these receptors remain attractive targets for the treatment of brain disorders, including alcohol use disorder (AUD). Here, we describe the most recent literature, with a primary focus on the past 5 years, on GPCR targets with the potential for reducing behaviours associated with excessive alcohol intake. Specifically, we focus on preclinical evidence of compounds with attractive pharmacological profiles and potential for future clinical investigation for the treatment of AUD.
ABSTRACT
Neuropeptides and G protein-coupled receptors (GPCRs) have long been, and continue to be, one of the most popular target classes for drug discovery in CNS disorders, including alcohol use disorder (AUD). Yet, orphaned neuropeptide systems and receptors (oGPCR), which have no known cognate receptor or ligand, remain understudied in drug discovery and development. Orphan neuropeptides and oGPCRs are abundantly expressed within the brain and represent an unprecedented opportunity to address brain function and may hold potential as novel treatments for disease. Here, we describe the current literature regarding orphaned neuropeptides and oGPCRs implicated in AUD. Specifically, in this review, we focus on the orphaned neuropeptide cocaine- and amphetamine-regulated transcript (CART), and several oGPCRs that have been directly implicated in AUD (GPR6, GPR26, GPR88, GPR139, GPR158) and discuss their potential and pitfalls as novel treatments, and progress in identifying their cognate receptors or ligands.
Subject(s)
Alcoholism , Central Nervous System Diseases , Neuropeptides , Humans , Alcoholism/drug therapy , Receptors, G-Protein-Coupled , LigandsABSTRACT
BACKGROUND: Pain is one of the most prevalent, costly and disabling conditions that reduces quality of life. Although there are many analgesics available, there is some concern regarding their efficacy, safety and side effects. Organic selenium compounds are attractive targets of various research groups due to their pharmacological properties. OBJECTIVES: The aim of this study was to evaluate the antinociceptive and anti-inflammatory activity of 1,2-bis-(4-methoxyphenylselanyl) styrene (BMOSE) in mice, as well as to investigate the mechanism involved in the antinociceptive effect. METHODS: The animals were submitted to the formalin and glutamate tests. The assessment of the possible involvement of the serotonergic system in BMOSE antinociceptive activity was performed using the glutamate test. Also, we investigated the possible toxicity of the compound. KEY FINDINGS: 1,2-bis-(4-methoxyphenylselanyl) styrene (0.1-50 mg/kg, i.g.) was efficient in avoiding nociception induced by glutamate and formalin and also reduced paw oedema. The possible involvement of 5-HT3 serotoninergic receptor antagonist ondansetron blocked the antinociceptive effect of BMOSE. The acute toxicity assays did not show any toxicity related to the administration of BMOSE (200 mg/kg). CONCLUSIONS: It is possible to conclude that BMOSE has both antinociceptive and anti-inflammatory activity, and the serotoninergic system, more specifically, the 5-HT3 receptor, is involved in the effect.
