Intranasal midazolam administration enhances amnesic effect in rats.
Intranasal midazolam administration enhances amnesic effect in rats.
复制标题
鼻内给予咪达唑仑可增强大鼠的遗忘作用。
DOI：
10.1007/s00540-016-2153-x
复制
发表时间：
2016
期刊：
影响因子：
2.8
通讯作者：
Yokoyama M.
中科院分区：
文献类型：
--
作者：
Kadono T;Kawano T;Yamanaka D;Tateiwa H;Urakawa M;Locatelli FM;Yokoyama M.
鼻内（i.n.）咪达唑仑的给药因其镇静、抗焦虑和抗惊厥作用而显示出有效和安全。然而，还没有调查的影响，i.n.咪达唑仑诱导的顺行性遗忘。此外，尽管从鼻直接给药至中枢神经系统（CNS）的潜力最近已成为非常感兴趣的话题，但仍不清楚该途径是否也参与i. n.咪唑安定在这项研究中，我们研究了i.n.与肌内（i.m.）给药对大鼠中咪达唑仑诱导的健忘症的影响。通过i.m或i. n给予等效剂量的0.6 mg/kg咪达唑仑。路线顺行性遗忘通过情境/线索恐惧条件反射测试进行评估。每只动物在给药后20分钟适应，然后在24小时后测试冻结反应。咪达唑仑通过任一途径给药产生相似水平的轻度镇静（最小自发活动）。然而，i. n.与i.m.相比，咪达唑仑给药诱导显著较少的冻结行为。咪唑安定此外，在大鼠中，在嗅觉毒性物质3-甲基吲哚给药后，来自嗅觉上皮的电输入被破坏，i.n.-未观察到咪达唑仑介导的增强遗忘作用。结果表明，肌注咪达唑仑可能通过苯二氮卓类受体向脑内传递嗅觉信号，与肌注咪达唑仑相比，肌注咪达唑仑可能通过苯二氮卓类受体向脑内传递嗅觉信号。给药后，可以产生更显著的遗忘作用，而不改变镇静水平。进一步的临床研究是必要的。
Intranasal (i.n.) administration of midazolam has been shown to be effective and safe for its sedative, anxiolytic, and anticonvulsant effects. However, there has been no investigation on the influence of i.n. administration on midazolam-induced anterograde amnesia. In addition, although the potential of direct drug delivery from the nose to the central nervous system (CNS) has recently become a topic of great interest, it remains unclear whether this pathway is also involved after i.n. midazolam. In this study, we examined the efficacy and the underlying mechanism of i.n. administration compared with intramuscular (i.m.) administration on midazolam-induced amnesia in rats. Equivalent doses of 0.6 mg/kg midazolam were administered via either the i.m or the i.n. route. Anterograde amnesia was assessed by a contextual/cued fear conditioning test. Each animal was conditioned 20 min after drug administration and then tested for a freezing response 24 h later. Midazolam administration by either route produced a similar level of light sedation (minimum spontaneous activity). However, i.n. administration of midazolam induced significantly less freezing behavior compared with i.m. midazolam. Furthermore, in rats with disrupted electrical input from the olfactory epithelium after an olfactotoxicant 3-methylindole administration, the i.n.-mediated enhanced amnesic effect of midazolam was not observed. Our findings indicate that i.n midazolam could probably generate olfactory signals to the brain via benzodiazepine receptors and, compared with i.m. administration, can produce a more significant amnesic effect without alteration in sedative levels. Further clinical studies are warranted.