Ceruletide (Caerulein)

Ceruletide, as a decapeptide and a potent cholecystokinetic agent, has a direct spasmogenic effect on the gallbladder muscle and bile ducts in humans and animals.^[1]

In vitro experiment it indicated that at 1, 10, and 100 nmol/L, cerulein induced NF-kB–binding activity in a dose-dependent. But 0.3 nmol/L cerulein had no effect on activation NF-kappaB/Rel.^[7]

In vivo, at a dose of 100 μg/kg, ceruletide decreased the rates of spontaneous locomotor activity and rearing, and also inhibited methylphenidate- and methamphetamine-induced hyperactivity in both sham-operated and vagotomized mice to same extent.^[2] In vivo efficacy test it shown that rabbits were treated with 8 and 50 μg/kg of ceruletide decreased the plasma homovanillic acid levels, but had no significant differences. 140 and 200 μg/kg ceruletide had remarkable reduction of plasma homovanillic acid.^[3] Ceruletide (100 μg/kg, s.c.) influenced the central dopaminergic system, enhanced the central effects of neuroleptics and had the potent therapeutic effects in the clinical trials.^[4] In a mouse hypoxia model, treatment with 1-100 μg/kg ceruletide subcutaneously obviously prevented the CO-induced impairment of performance and the amelioration being correlated with the severity of hypoxia.^[5] In addition, treatment with 10-300 μg/kg intraperitoneally ceruletide slightly but remarkably decreased the response rate (frequency of shuttles) under a discrete avoidance task in mice.^[6]

References:
[1].Vincent ME, et al. Pharmacology, clinical uses, and adverse effects of ceruletide, a cholecystokinetic agent. Pharmacotherapy. 1982 Jul-Aug;2(4):223-34.
[2].Moroji T, Hagino Y. Bilateral subdiaphragmatic vagotomy does not prevent the behavioral effects of systematically administered ceruletide in mice. Neuropeptides. 1987 Apr;9(3):217-24.
[3].Wakata N, et al. Effect of ceruletide on plasma monoamine metabolites in the rabbit. J Neurol Sci. 1991 May;103(1):97-100
[4].Hagino Y, Moroji T. Effect of ceruletide on discriminated avoidance behavior in rats. Neuropeptides. 1987 Nov-Dec;10(4):335-42.
[5].Maurice T, et al. Cholecystokinin-related peptides, after systemic or central administration, prevent carbon monoxide-induced amnesia in mice. J Pharmacol Exp Ther. 1994 May;269(2):665-73.
[6].Kuribara H, et al. Effects of ceruletide, administered singly and in combination with central-acting drugs, on discrete shuttle avoidance response in mice. Jpn J Pharmacol. 1990 Nov;54(3):325-9.
[7].Steinle AU, et al. NF-kappaB/Rel activation in cerulein pancreatitis. Gastroenterology. 1999 Feb;116(2):420-30.

Ceruletide 作为一种十肽和一种有效的胆囊收缩剂,对人类和动物的胆囊肌肉和胆管具有直接的痉挛作用。^[1]

体外实验表明,在 1、10 和 100 nmol/L 时,雨蛙素以剂量依赖性方式诱导 NF-kB 结合活性。但0.3 nmol/L的雨蛙素对激活NF-kappaB/Rel没有影响。^[7]

在体内,在 100 μg/kg 的剂量下,ceruletide 降低了假手术和迷走神经切断小鼠的自发运动活动和饲养率,并且还在相同程度上抑制了哌醋甲酯和甲基苯丙胺诱导的多动症。^[2] 体内药效试验表明,兔用8和50μg/kg的ceruletide处理后血浆高香草酸水平降低,但无显着差异。 140和200 μg/kg ceruletide显着降低血浆高香草酸。^[3] Ceruletide (100 μg/kg, s.c.)影响中枢多巴胺能系统,增强精神安定药的中枢作用,具有强效临床试验中的疗效。^[4] 在小鼠缺氧模型中,皮下注射 1-100 μg/kg 的 ceruletide 可明显防止 CO 引起的性能损害,并且改善与严重程度相关^[5]此外,用 10-300 μg/kg 腹腔注射 ceruletide 治疗小鼠在离散回避任务下的反应率（穿梭频率）略有但显着降低。^{[ 6]}