PA-9

PA-9 is a pituitary adenylate cyclase-activating polypeptide (PACAP) type I (PAC1) receptor antagonist. PA-9 dose dependently inhibits PACAP-induced cAMP elevation with an IC50 of 5.6 nM. PA-9 can be used for the research of neuropathic and/or inflammatory pain[1].

Signaling Pathways >> Others >> Others

Research Areas >> Inflammation/Immunology

Research Areas >> Neurological Disease

PAC1 receptor

PA-9 (10 pM to 10 nM; 30 minutes) dose dependently inhibits PACAP-induced (1 nM) CREB phosphorylation in the CHO cells expressing PAC1 receptors[1].

PA-9 (100 pmol; co-injection with PACAP) attenuates the development of PACAP-induced (100 pmol/5 μL; intrathecal injection) aversive responses of mice[1]. PA-9 (100 pmol; co-injection with PACAP) significantly blocks the induction of PACAP-induced (100 pmol) mechanical allodynia[1]. PA-9 (100 pmol/5 μl; single intrathecal injection alone) does not induce aversive responses and mechanical allodynia of mice[1]. PA-9 is well accommodated in the subpocket formed by L80, F81, I83, G91, V92, P107, A112, and C113 of the PAC1 receptor, precipitating in hydrophobic interactions[1]. Animal Model: Male ddY mice (6 weeks old at the start of experiments; intrathecal injection 100 pmol/5 μL PACAP)[1] Dosage: intrathecal injection, co-injection with PACAP. Administration: 100 pmol/5 μL Result: Attenuated the development of PACAP-induced aversive responses. Blocked the induction of PACAP-induced mechanical allodynia.

[1]. Takasaki I, et al. In Silico Screening Identified Novel Small-molecule Antagonists of PAC1 Receptor. J Pharmacol Exp Ther. 2018 Apr;365(1):1-8.