SCH 58261 is a potent and selective non-xanthine A2A adenosine antagonist, with an IC50 of 15nM[1]. SCH 58261 has been widely used in animal models of cardiovascular and neurological regulation[2].
In vitro, SCH 58261 treatment (50nM; 24h) reduced microglia proliferation as well as the expression and release of pro-inflammatory mediators in rat retinal nerve cell culture[3].
In vivo, SCH 58261 treatment at a single dose of 5mg/kg (i.p.) for 90min reversed reserpine-induced muscle stiffness and attenuated reserpine-enhanced tonic and reflex electromyographic activity in gastrocnemius and tibial muscles[4]. Systemic administration of SCH 58261 (5mg/kg; i.p.; 3 times, every 3h, 10min before haloperidol) within one day partially decreased the haloperidol-induced catalepsy and the increase in the proenkephalin (PENK) expression in both dorsolateral and ventrolateral parts of the striatum of rats[5]. In rats, intraperitoneal injection of SCH 58261 at a single dose of 10mg/kg for one day enhanced exercise capacity, increased alertness, and slightly increased blood pressure and heart rate[6]. Intraperitoneal injection of SCH 58261 (0.01mg/kg) administered 5 minutes after middle cerebral artery occlusion (MCAO) inhibited turning behavior in rats and significantly reduced the outflow of glutamate, markedly decreasing cortical damage without preventing sensorimotor impairment[7].
References:
[1] Zocchi C, Ongini E, Conti A, et al. The non-xanthine heterocyclic compound SCH 58261 is a new potent and selective A2a adenosine receptor antagonist[J]. The Journal of pharmacology and experimental therapeutics, 1996, 276(2): 398-404.
[2] Monopoli A, Casati C, Lozza G, et al. Cardiovascular pharmacology of the A2A adenosine receptor antagonist, SCH 58261, in the rat[J]. The Journal of pharmacology and experimental therapeutics, 1998, 285(1): 9-15.
[3] Aires I D, Boia R, Rodrigues‐Neves A C, et al. Blockade of microglial adenosine A2A receptor suppresses elevated pressure‐induced inflammation, oxidative stress, and cell death in retinal cells[J]. Glia, 2019, 67(5): 896-914.
[4] Wardas J, Konieczny J, Lorenc‐Koci E. SCH 58261, an A2A adenosine receptor antagonist, counteracts parkinsonian‐like muscle rigidity in rats[J]. Synapse, 2001, 41(2): 160-171.
[5] Wardas J, Pietraszek M, Dziedzicka-Wasylewska M. SCH 58261, a selective adenosine A2A receptor antagonist, decreases the haloperidol-enhanced proenkephalin mRNA expression in the rat striatum[J]. Brain research, 2003, 977(2): 270-277.
[6] Ongini E. SCH 58261: A selective A2A adenosine receptor antagonists[J]. Drug development research, 1997, 42(2): 63-70.
[7] Melani A, Pantoni L, Bordoni F, et al. The selective A2A receptor antagonist SCH 58261 reduces striatal transmitter outflow, turning behavior and ischemic brain damage induced by permanent focal ischemia in the rat[J]. Brain Research, 2003, 959(2): 243-250.
SCH 58261是一种强效选择性非黄嘌呤类A2A腺苷受体拮抗剂，IC50值为15nM[1]。SCH 58261已广泛应用于心血管和神经调节的动物模型研究[2]。
在体外，50nM浓度的SCH 58261处理24小时可抑制大鼠视网膜神经细胞培养物中小胶质细胞的增殖，并减少促炎介质的表达和释放[3]。
在体内，单次腹腔注射5mg/kg剂量的SCH 58261 90分钟后，能逆转利血平诱导的肌肉僵硬，并减轻利血平增强的腓肠肌和胫骨肌强直及反射性肌电活动[4]。一日内以5mg/kg剂量腹腔注射三次SCH 58261（每次间隔3小时，于氟哌啶醇给药前10分钟注射），可部分缓解氟哌啶醇诱导的大鼠纹状体背外侧和腹外侧区的强直症及前脑啡肽原（PENK）表达升高[5]。单次腹腔注射10mg/kg剂量的SCH 58261一天后，可增强大鼠的运动能力、提高警觉性，并轻微升高血压和心率[6]。在大脑中动脉闭塞（MCAO）后5分钟腹腔注射0.01mg/kg剂量的SCH 58261，能抑制大鼠翻身行为，显著减少谷氨酸流出，明显减轻皮质损伤，无法改善感觉运动功能障碍[7]。