α,β-Methylene-ATP (trisodium)

α,β-Methylene-ATP trisodium is an agonist of P2X1 and P2X3 receptors and can cross the blood-brain barrier. α,β-Methylene-ATP trisodium can trigger a reflex pressor response by activating P2X receptors in peripheral muscles and the central locus coeruleus (LC); this effect can be blocked by the P2X antagonist PPADS (HY-108960). α,β-Methylene-ATP trisodium also activates noradrenergic neurons in the central locus coeruleus, mediating antinociceptive effects; this effect can be attenuated by the locus coeruleus damaging agent DSP-4 (HY-103210/HY-121602). α,β-Methylene-ATP trisodium can be used to study the pathological mechanisms of neuropathic pain, cardiovascular reflex regulation, and antinociceptive effects of the central nervous system^[1][2][3]. In Vitro:Electrophysiological activity: α,β-Methylene-ATP trisodium (10 μM; 3 seconds) evokes a fast inward current in rat dorsal root ganglion (DRG) neurons, associated with P2X3 receptor activation. 10 μM Diinosine pentaphosphate (Ip5I) can significantly inhibit this inward current^[1].
α,β-Methylene-ATP trisodium (10 μM; transient) enhances the amplitude of the current evoked by Acetylcholine (HY-B0282) in rat adrenal medullary chromaffin cells and increases the proportion of the current sensitive to α-conotoxin RgIA (HY-P5845)^[1].
In Vivo:α,β-Methylene-ATP (5-50 μg/kg; left popliteal artery injection; single dose) trisodium induces a reflex pressor response in the decerebrate cat model, which is blocked by sciatic nerve transection or the P2X receptor antagonist PPADS (HY-108960) (10 mg/kg; left popliteal artery injection)^[2].
α,β-Methylene-ATP (10 nmol/rat; intracerebroventricular injection; single dose) trisodium produces an anti-mechanical nociceptive effect in Sprague-Dawley rats, which is significantly attenuated by pretreatment with DSP-4 (HY-121602/HY-103210) (10 mg/kg DSP-4; intraperitoneal injection)^[3].
α,β-Methylene-ATP (0.1-1 nmol/side; bilateral microinjection into the locus coeruleus; single dose) trisodium increases the pain threshold of Sprague-Dawley rats in a dose-dependent manner, an effect that could be antagonized by co-injection of PPADS (HY-108960) (0.1-1 nmol/side)[3].