Dopamine D1 receptor is a G protein-coupled receptor that is one of the dopamine receptors. It exhibits cognitive functions such as memory and attention controlled by dopamine. Specifically, it regulates memory, learning, and neuronal growth. On the other hand, it plays an important role in regulating functions such as movement, emotion, cognition, and reward. Parkinson’s disease is a neurodegenerative disorder primarily caused by the loss of dopaminergic neurons in the substantia nigra midbrain. However, the dopamine D1 receptor is enriched in the hypothalamic nucleus and midbrain. Meanwhile, it regulates the reward mechanisms and the development of addiction. Thus, dopamine D1 receptor agonists have the potential to improve dyskinesias and other symptoms in Parkinson’s disease patients. We’ll introduce a potent D1 receptor agonist, A-77636.

A-77636 is an orally active, selective, and long-acting dopamine agonist (EC50=1.1 nM).

A-77636 selectively targets dopamine D1 receptors, showing high affinity (Ki=39.8 nM). Therefore, in different animal models, A-77636 has shown potency to increase locomotor activity and reduce Parkinsonian symptoms. Firstly, in a 6-OHDA injury model, it (0-3.2 μmol/kg; s.c.; single dose) is able to induce rotational behavior in rats. Also produces forelimb clonus in rats and mice with EC50s of 12.3 μmol/kg and 12.1 μmol/kg, respectively. It (1-10 mg/kg; ip; single dose) also attenuates the addictive agent-inducing effect in Swiss-Webster mice, and the effect is sustained. A-77636 (0.5, 1.0, or 2.0 μmol/kg; p.o.; single dose) increases locomotor activity and reduces the severity of Parkinson-like symptoms.

In summary, A-77636 is a potent D1 receptor agonist with potential to alleviate Parkinson’s disease. It is also effective in modulating reward mechanisms and addiction development.


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