Kleinloog Daniël, Uit den Boogaard Anna, Dahan Albert, Mooren René, Klaassen Erica, Stevens Jasper, Freijer Jan, van Gerven Joop
Centre for Human Drug Research, Leiden, The Netherlands
Centre for Human Drug Research, Leiden, The Netherlands.
J Psychopharmacol. 2015 Apr;29(4):401-13. doi: 10.1177/0269881115570082. Epub 2015 Feb 17.
The psychomimetic effects that occur after acute administration of ketamine can constitute a model of psychosis and antipsychotic drug action. However, the optimal dose/concentration has not been established and there is a large variety in outcome measures. In this study, 36 healthy volunteers (21 males and 15 females) received infusions of S(+)-ketamine or placebo to achieve pseudo-steady state concentrations of 180 and 360 ng/mL during two hours. The target of 360 ng/mL induced increasingly more intensive effects than expected, and the targets were subsequently reduced to 120 and 240 ng/mL, which were considered tolerable. There was a clear, concentration-dependent psychomimetic effect as shown on all subscales of the positive and negative syndrome scale (e.g. positive subscale +43.7%, 95%CI 34.4-53.7%, p < 0.0001 for 120 ng/mL and +70.5%, 95%CI 59.0-82.8%, p < 0.0001 for 240 ng/mL) and different visual analogue scales. The startle reflex was inhibited (prepulse inhibition) by both main target concentrations to a similar extent, suggesting a maximum effect. Ketamine was found to constitute a robust model for induction of psychomimetic symptoms and the optimal concentration range for a drug interaction study would be between 100 and 200 ng/mL.
氯胺酮急性给药后出现的拟精神病效应可构成一种精神病和抗精神病药物作用的模型。然而，最佳剂量/浓度尚未确定，且结果测量存在很大差异。在本研究中，36名健康志愿者（21名男性和15名女性）接受了S(+)-氯胺酮或安慰剂输注，以在两小时内达到180和360 ng/mL的伪稳态浓度。360 ng/mL的目标浓度诱导的效应比预期更强烈，随后目标浓度降至120和240 ng/mL，这被认为是可耐受的。在阳性和阴性症状量表的所有子量表上均显示出明显的浓度依赖性拟精神病效应（例如，阳性子量表在120 ng/mL时为+43.7%，95%CI 34.4-53.7%，p < 0.0001；在240 ng/mL时为+70.5%，95%CI 59.0-82.8%，p < 0.0001）以及不同的视觉模拟量表。两种主要目标浓度对惊跳反射（前脉冲抑制）的抑制程度相似，表明达到了最大效应。发现氯胺酮是诱导拟精神病症状的可靠模型，药物相互作用研究的最佳浓度范围为100至200 ng/mL。
