Dopamine (DA) is a catecholamine neurotransmitter. Dopamine participates in the regulation of nervous system movement and neuroendocrine. Besides, many studies have found that dopamine participates in the regulation of immune function. D1-like receptor is a kind of dopamine receptor, including D1 and D5 receptor subtypes. No doubt, D1-like receptor agonist can promote dopamine to play a positive role.
σ-1 receptor is a chaperone protein that interacts with other proteins, such as N-methyl-D-aspartate receptors (NMDARs), to regulate ion channels. The same as dopamine, σ-1 can be used for the research of nervous system disease. Obviously, σ-1 modulator can regulate σ-1 to make it develop a beneficial role in human.
SKF83959 is a potent and selective D1-like receptor partial agonist and an allosteric of σ-1 modulator. The Ki values for rat D1 and D5 receptors are 1.18 nM and 7.56 nM, respectively. Interestingly, SKF83959 belongs to benzazepine family has improvements on cognitive dysfunction. For example, a research found that SKF83959 has anti-amnesic activities and restores brain-derived neurotrophic factor (BDNF) signaling pathway in the hippocampus in mice. Certainly, the results suggest that SKF83959 It is a good choice for the treatment of Alzheimer’s disease. In vitro, SKF83959 (10~250 μM) stimulates phosphatidylinositol bisphosphate (PIP2) hydrolysis in membranes. Consequently, these show that the significant roles for D1-like receptor and σ-1 and the selectivity of SKF83959.
In conclusion, SKF83959 is a selective D1-like receptor partial agonist and an allosteric of σ-1 modulator. SKF83959 could be used for the research of Alzheimer’s disease.