早期的临床经验与小说NMDA受体拮抗剂CNS 5161。

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沃尔特先生,布拉德福德美联社,费舍尔J,利兹KR

早期的临床经验与小说NMDA受体拮抗剂CNS 5161。

Br中国新药杂志。2002年3月,53(3):305 - 11所示。

PubMed ID

11874394 (在PubMed

]

文摘

目的:探讨安全、耐受性和药物动力学的小说NMDA拮抗剂CNS 5161年的人类。谷氨酸受体的过度激活,尤其是的n -甲基- d (NMDA)亚型与神经性疼痛有关,和大脑局部缺血造成的损害在成熟的大脑或者hypoxia-ischaemia (HI)在新生儿。中枢神经系统5161是一种新型门冬氨酸离子通道拮抗剂与NMDA受体和离子通道交互网站产生一个非竞争性的封锁谷氨酸的行动。临床前研究表明神经中枢神经系统的影响5161成年大鼠局灶性脑缺血模型,以及抗惊厥的镇痛效果。该研究报告的第一个政府CNS 5161人。其目标是调查的血液动力学的影响,评估其安全性和耐受性在健康男性志愿者,并提供一些初步的人体药代动力学数据。方法:我们进行了一个随机、双盲安慰剂对照第一阶段5161剂量升级研究中枢神经系统。志愿者被随机分配接受CNS 5161或安慰剂3:1的比例。24收到的32名健康志愿者进行静脉输液的CNS 5161超过15分钟,随后连续测量血浆药物浓度和血液动力学的观察24 h。剂量升级设计采用和志愿者分层分为八个剂量组,从30 microg 2000 microg。结果:药物被接受者耐受性良好。 Side-effects were dose-related, self limiting and comprised minor subjective sensory symptoms. A dose dependent rise in systolic, mean arterial and diastolic blood pressure was seen in subsequent dosage groups, reaching 23/19 mmHg. Maximal effects were seen between 60 and 120 min after commencement of infusion. All subjects returned to baseline haemodynamic values within 24 h. Putative neuroprotective concentrations of CNS 5161 were achieved transiently, although these levels were not sustained. The pharmacokinetic data were best described by a two compartment model. The mean half-life was 2.95 h (s.d. 0.75). Mean clearance was 106 l h(-1) (s.d. 17.8) mean volume of distribution was 296 l (s.d. 69). These parameters were not significantly affected by body weight. CONCLUSIONS: This study suggests that CNS 5161 is well tolerated in healthy volunteers within the dose range studied. In addition, information concerning the pharmacokinetics of the compound has been acquired. Studies to investigate the efficacy of the compound in man may now be justified.

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药物

cns - 5161