ABT 702 dihydrochloride is a novel, potent non-nucleoside adenosine kinase (AK) inhibitor with an IC50 values of 1.7nM [1]. ABT 702 increases extracellular adenosine concentrations at sites of tissue trauma thereby attenuates neuronal response [1]. ABT 702 has therapeutic potential as analgesic and anti-inflammatory agents [1].
In vitro, treatment of ABT 702 (3μM) to the isolated neonatal rat spinal cord for 20 minutes, gradually decreased slow ventral root potentials (VRP) with a slight decline in monosynaptic reflex potentials (MSR), leading to the inhibition of spinal nociceptive transmission [2]. ABT 702 highly inhibited AK activity in IMR-32 cells with an IC50 value of 1.7nM [1]. ABT 702 (20μM) attenuated p-ERK1/2 and p-P38 activation in LPS induced activated mouse microglia cells (EOC-20) [3].
In vivo, ABT 702 reduced acute somatic nociception in the mouse hot-plate assay following oral administration of 65μmol/kg or intraperitoneal injection of 8μmol/kg [1]. ABT 702 decreased regional FDG levels in the rat cerebellum, pons, mesencephalic region and medulla, via intraperitoneal (i.p.) injection of 3mg/kg [4]. Subcutaneous injection of ABT 702 (10mg/kg) for 1 hour significantly reduced the electrical evoked responses of spinal neurons in spiral never ligation (SNL) rats, thus demonstrating effective analgesia [5].
References:
[1] Jarvis MF, Yu H, Kohlhaas K, et al. ABT-702 (4-amino-5-(3-bromophenyl)-7-(6-morpholinopyridin-3-yl) pyrido [2, 3-d] pyrimidine), a novel orally effective adenosine kinase inhibitor with analgesic and anti-inflammatory properties: I. In vitro characterization and acute antinociceptive effects in the mouse. J Pharmacol Exp Ther.2000;295(3):1156-1164.
[2] Otsuguro K, Tomonari Y, Otsuka S, Yamaguchi S, Kon Y, Ito S. An adenosine kinase inhibitor, ABT-702, inhibits spinal nociceptive transmission by adenosine release via equilibrative nucleoside transporters in rat. Neuropharmacology.2015;97:160-170.
[3] Ahmad S, Elsherbiny NM, Bhatia K, Elsherbini AM, Fulzele S, Liou GI. Inhibition of adenosine kinase attenuates inflammation and neurotoxicity in traumatic optic neuropathy. J Neuroimmunol. 2014;277(1-2):96-104.
[4] Parkinson FE, Paul S, Zhang D, Mzengeza S, Ko JH. The Effect of Endogenous Adenosine on Neuronal Activity in Rats: An FDG PET Study. J Neuroimaging. 2016;26(4):403-405.
[5] Suzuki R, Stanfa LC, Kowaluk EA, Williams M, Jarvis MF, Dickenson AH. The effect of ABT-702, a novel adenosine kinase inhibitor, on the responses of spinal neurones following carrageenan inflammation and peripheral nerve injury. Br J Pharmacol. 2001;132(7):1615-1623.
ABT 702 dihydrochloride是一种新型、高效的非核苷类腺苷激酶（AK）抑制剂，其IC50值为1.7nM [1]。ABT 702能够在组织损伤部位提高细胞外腺苷浓度，从而减轻神经元反应 [1]。ABT 702具有作为镇痛剂和抗炎剂的治疗潜力 [1]。
在体外，3μM的ABT 702处理20分钟能有效降低分离的新生大鼠脊髓慢型腹侧神经根电位（VRP），轻微降低单突触反射电位（MSR），抑制脊髓的疼痛传递 [2]。ABT 702能高效抑制神经母瘤细胞（IMR-32）中的AK活性，其IC50值为1.7nM [1]。20μM的ABT 702能减弱被LPS诱导的活化小鼠小胶质细胞（EOC-20）中p-ERK1/2和p-P38的激活 [3]。
在体内，每日口服65μmol/kg的ABT 702或腹腔注射8μmol/kg的ABT 702，能减弱小鼠热板实验中的急性躯体疼痛 [1]。腹腔注射3mg/kg剂量的ABT-702能降低大鼠小脑、脑桥、中脑区域和延髓的局部 FDG 水平 [4]。给螺旋神经节结扎处理（SNL）的大鼠皮下注射剂量为10mg/kg的ABT 702，其脊髓神经元的电诱发反应显著降低，显示出有效的镇痛效果[5]。