PPADS

PPADS is a P2X receptor (P2X Receptor) antagonist and a reversible competitive antagonist of NAADP receptors, with IC₅₀ values of 68 nM (P2X1) and 214 nM (P2X3), respectively. PPADS alleviates pain-related behaviors in the central and peripheral nervous systems of mice after peripheral neuropathy, inhibits the overproduction of IL-1β, IL-6, iNOS and nNOS, and suppresses the hydrolytic activity of extracellular ATPase. PPADS blocks ATP-mediated inward currents on recombinant rat P2X₁ and P2X₃ receptors, and inhibits purinergic nerve stimulation-induced contraction of rabbit bladder detrusor muscle. PPADS is applicable to research related to neuropathic pain^[1][2][3][4]. In Vitro:PPADS (1-100 μM; 1 min) acts as a competitive, partially surmountable antagonist of NAADP (HY-103317)-induced Ca²⁺ release in sea urchin egg homogenate, with an IC₅₀ of 20.6 μM^[2].
PPADS (100 μM) inhibits the transport of NAADP into NIH-3T3 cells, with an inhibition rate of 31.1%^[2].
PPADS (0.01-30,000 nM; 20 min) potently inhibits ATP (HY-B2176)-evoked inward currents at rat P2X₁ and P2X3 receptors expressed in Xenopus laevis oocytes via non-competitive antagonism (partially reversible after washing), with IC₅₀ values of 68.5 nM and 213.6 nM, respectively^[3].
PPADS (1-30 μM; for at least 20 min) concentration-dependently antagonizes the α,β-methylene ATP-induced contraction of rabbit urinary bladder detrusor muscle mediated by P_2x-purinergic receptors^[4].
PPADS (1-30 μM; at least 20 min) concentration-dependently antagonizes purinergic neurogenic contractions of rabbit detrusor muscle^[4]. In Vivo:PPADS (i.p.; once daily; 11 days (chronic); single administration (acute, on day 3 or day 14 post-injury), 6.25-25 mg/kg) dose-dependently reverses neuropathic pain behaviors in CCI mice. The 25 mg/kg dose fully restores physiological nociceptive thresholds, and simultaneously normalizes the abnormal expressions of proinflammatory cytokines, nitric oxide synthase, NF-κB and myelin proteins in peripheral and central pain signaling pathways^[1].