Dopamine Receptors are a class of G protein-coupled receptors, widely exist in the brain. There are at least five subtypes of dopamine receptors, D1, D2, D3, D4, and D5. The D1 and D5 receptors are members of the D1-like family of dopamine receptors, whereas the D2, D3 and D4 receptors are members of the D2-like family. Importantly, dopamine receptors are implicated in many neurological processes, including motivation and drive and cognition. What’s more, abnormal dopamine receptor signaling and dopaminergic nerve function are inseparable from several psychiatric disorders. Thus, dopamine receptors are common neurologic drug targets. For example, antipsychotics are often dopamine receptor antagonists, while psychostimulants are typically indirect agonists of dopamine receptors.

The D1-like receptors are a subfamily of dopamine receptors that bind the endogenous neurotransmitter dopamine. D1-like subfamily consists of two G protein-coupled receptors, D1 and D5. They mediate excitatory neurotransmission by coupling to Gs. Pharmacological studies indicate that D1 and D5 receptors play an important role in cognitive function. In addition, there is an inseparable relationship between D1 receptor and the cognitive deficits observed during the disease. Therefore, D1 has been the focus of past schizophrenia research. The D5 receptor has a 10-fold higher affinity for dopamine than the D1 subtype. Importantly, the D5 receptor play an important role in working memory and related PFC functioning.

SKF83959 is a partial agonist of dopamine D1-like receptor and a σ-1 receptor modulator.

SKF83959 acts as a potent and selective agonist at the D1 and D2 receptor. And it is also a σ-1 receptor modulator. Importantly, SKF83959 reverses the Scopolamine-induced cognitive impairments. It also has anti-amnesic activity. What’s more, SKF83959 can restore the brain-derived neurotrophic factor signaling pathway. SKF83959 has potential in the research for Alzheimer’s disease and depression.

All in all, SKF83959 is a D1-like receptor partial agonist and a σ-1 receptor modulator.


[1] Martel JC, et, al. Front Pharmacol. 2020 Jul 14;11:1003.

[2] Carr GV, et, al. Front Pharmacol. 2017 Oct 6;8:666.