α2 adrenoceptor is a G protein-coupled receptor (GPCR) associated with the Gi heterotrimeric G-protein. Besides, the α2 adrenoceptor is activated by the catecholamines norepinephrine and epinephrine. Furthermore, alpha-2A, alpha-2B, and alpha-2C are the subtypes of the alpha-2 adrenoceptor. Additionally, These receptors have a critical role in regulating neurotransmitter release from sympathetic nerves and adrenergic neurons in the central nervous system.
ARC 239 (10 µM) shows α2B/2C adrenoceptor antagonist activity with Pkd values of 5.95, 7.41, and 7.56 for α2A, α2B, α2C subtypes, respectively. Besides, ARC 239 binds to CHO cell membranes expressing human recombinant α2A, α2B, and α2C subtypes with Pki values of 5.60, 8.40, and 7.08, respectively. What’s more, ARC 239 displays a low potency against BHT-920 with a pKb value of 6.3.
ARC 239 also shows activity in vivo.
ARC 239 shows a strong inhibitory effect on noradrenaline-stimulated contractions. Besides, In the stretching test, ARC 239 increases the cervical resistance on pregnancy days 18 and decreases on 20 days. But ARC 239 shows no effects on the 22-day pregnant cervical samples. Moreover, ARC 239 has the potential for the research of premature labour. Additionally, ARC 239 shows inhibition to [3H]8-OH-DPAT and [3H]RX 821002 in membranes of rat brain cortex and hippocampus with Ki values of 63.1, 136 nM, respectively. As a result, ARC 239 also is a potent 5-HTIA receptor agonist.
In conclusion, ARC 239 is a selective α2B/2C adrenoceptor antagonist and also is a 5-HTIA receptor agonist. Besides, ARC 239 shows a strong inhibitory effect on noradrenaline-stimulated contractions. Moreover, ARC 239 has the potential for research on premature labour.