Saclofen is an orally competitive GABAB receptor antagonist, with an IC50 value of 7.8µM[1]. Saclofen attenuates the reduction of NO2-and NO3- without affecting nitric oxide (NO) releases in the rat striatum [2]. Saclofen is widely used to inhibit μ opioid agonist-induced feeding elicited from the nucleus accumbens shell in rats [3].
In vitro, Saclofen treatment at 100µM for 2 days regulated the migration of bromodeoxyuridine (BrdU)-positive rat cortical cells, resulting in the occurrence of cell aggregation[4].
In vivo, Saclofen treatment at a single dose of 50μg/10μl/rat (i.c.) for 60 minutes reduced the increase of serum TNF-α and IL-6 induced by lipopolysaccharide (LPS), and alleviated the inflammatory response in rats[5]. Five minutes before the injection of zymosan (30μg), intrathecal administration of Saclofen (1μg/5μl) significantly reduced the formation of knee joint edema in mice, and reduced the intra-articular levels of TNF-α and IL-1β[6].
References:
[1] Drew C A, Johnston G A R, Kerr D I B, et al. Inhibition of baclofen binding to rat cerebellar membranes by phaclofen, saclofen, 3-aminopropylphosphonic acid and related GABAB receptor antagonists[J]. Neuroscience letters, 1990, 113(1): 107-110.
[2] Adachi Y U, Kimura-Kuroiwa K, Kobayashi A, et al. The propofol-induced inhibition of nitric oxide release in rats brain was antagonized by perfusion of saclofen, GABAB receptor antagonist, using in vivo microdialysis experiment: 7AP4-8[J]. European Journal of Anaesthesiology| EJA, 2011, 28: 105.
[3] Znamensky V, Echo J A, Lamonte N, et al. γ-Aminobutyric acid receptor subtype antagonists differentially alter opioid-induced feeding in the shell region of the nucleus accumbens in rats[J]. Brain research, 2001, 906(1-2): 84-91.
[4] Behar T N, Schaffner A E, Scott C A, et al. GABA receptor antagonists modulate postmitotic cell migration in slice cultures of embryonic rat cortex[J]. Cerebral Cortex, 2000, 10(9): 899-909.
[5] Sallam M Y, El-Gowilly S M, Abdel-Galil A G A, et al. Central GABAA receptors are involved in inflammatory and cardiovascular consequences of endotoxemia in conscious rats[J]. Naunyn-Schmiedeberg's archives of pharmacology, 2016, 389(3): 279-288.
[6] Bassi G S, do C. Malvar D, Cunha T M, et al. Spinal GABA-B receptor modulates neutrophil recruitment to the knee joint in zymosan-induced arthritis[J]. Naunyn-Schmiedeberg's archives of pharmacology, 2016, 389(8): 851-861.
Saclofen是一种口服竞争性GABAB受体拮抗剂，IC50值为7.8µM[1]。Saclofen能减轻大鼠纹状体中NO2-和NO3-的减少，而不影响一氧化氮（NO）的释放[2]。Saclofen被广泛用于抑制大鼠伏隔核壳区μ阿片受体激动剂诱导的进食行为[3]。
在体外，使用100µM的Saclofen处理2天，调节了溴脱氧尿苷（BrdU）阳性大鼠皮层细胞的迁移，导致细胞聚集的发生[4]。
在体内，单次给予50µg/10µl/只大鼠（脑室内注射）剂量的Saclofen处理60分钟，降低了脂多糖（LPS）诱导的血清TNF-α和IL-6的升高，并减轻了大鼠的炎症反应[5]。在注射酵母聚糖（30µg）前5分钟，鞘内给予Saclofen（1µg/5µl）显著减少了小鼠膝关节水肿的形成，并降低了关节腔内TNF-α和IL-1β的水平[6]。