File S E, Pellow S, Wilks L
Psychopharmacology (Berl). 1985;85(3):295-300. doi: 10.1007/BF00428190.
The effects of CL 218,872, initially classified as a non-sedative anxiolytic, were investigated and compared with those of chlordiazepoxide in the holeboard. The ability of two drugs that antagonise the effects of benzodiazepines, CGS 8216 and Ro 15-1788, to reverse the effects of CL 218,872 and chlordiazepoxide were also investigated, to see whether their effects might be mediated via benzodiazepine receptors. CL 218,872 (10 mg/kg) was found to be significantly sedative in both mice and rats (i.e., both locomotor activity and head-dipping were significantly decreased). In mice, the effects of CL 218,872 and of chlordiazepoxide were very similar over a range of doses, except that the stimulatory effect seen with low doses of chlordiazepoxide on head-dipping just failed to reach significance with CL 218,872. This study is in agreement with recently published results from different tests showing that sedative effects can be obtained with doses of CL 218,872 that are low and not much higher than those leading to anxiolysis. The sedative effects of both CL 218,872 (10 mg/kg) and chlordiazepoxide (20 mg/kg) were significantly reversed by RO 15-1788 (10 and 20 mg/kg) and CGS 8216 (10 mg/kg), suggesting that their effects are mediated via benzodiazepine receptors. The increase in head-dipping seen with chlordiazepoxide (2.5 mg/kg) was also reversed by RO 15-1788 and CGS 8216.
最初被归类为非镇静性抗焦虑药的CL 218,872的作用在跳台实验中进行了研究，并与氯氮卓的作用进行了比较。还研究了两种拮抗苯二氮卓类药物作用的药物CGS 8216和Ro 15-1788逆转CL 218,872和氯氮卓作用的能力，以观察它们的作用是否可能通过苯二氮卓受体介导。发现CL 218,872（10毫克/千克）对小鼠和大鼠均有显著的镇静作用（即自发活动和探头次数均显著减少）。在小鼠中，CL 218,872和氯氮卓在一系列剂量下的作用非常相似，只是低剂量氯氮卓对探头的刺激作用在CL 218,872作用下未达到显著水平。这项研究与最近发表的不同实验结果一致，表明使用低剂量的CL 218,872（并不比导致抗焦虑作用的剂量高多少）就能产生镇静作用。RO 15-1788（10和20毫克/千克）和CGS 8216（10毫克/千克）能显著逆转CL 218,872（10毫克/千克）和氯氮卓（20毫克/千克）的镇静作用，这表明它们的作用是通过苯二氮卓受体介导的。氯氮卓（2.5毫克/千克）引起的探头次数增加也能被RO 15-1788和CGS 8216逆转。
