D-Amphetamine Rapidly Reverses Dexmedetomidine-Induced Unconsciousness in Rats.
D-Amphetamine Rapidly Reverses Dexmedetomidine-Induced Unconsciousness in Rats.
复制标题
DOI：
10.3389/fphar.2021.668285
复制
发表时间：
2021
影响因子：
5.6
通讯作者：
Solt K
中科院分区：
文献类型：
--
作者：
Kato R;Zhang ER;Mallari OG;Moody OA;Vincent KF;Melonakos ED;Siegmann MJ;Nehs CJ;Houle TT;Akeju O;Solt K
d -安非他明诱导大鼠七氟醚和异丙酚麻醉苏醒。右美托咪定是一种α2-肾上腺素受体激动剂，通常用于程序性镇静，而氯胺酮是一种主要通过抑制nmda型谷氨酸受体起作用的麻醉剂。这些药物与异丙酚和挥发性麻醉剂具有不同的分子作用机制，可增强GABAA受体介导的抑制性神经传递。在这项研究中，我们测试了d-安非他明加速右美托咪定和氯胺酮后意识恢复的假设。16只大鼠（雄性8只，雌性8只）采用随机、盲法、交叉实验设计，所有药物均静脉给药。另外6只在前额皮质（PFC）预先植入电极的大鼠被用来分析神经生理学的变化。右美托咪定后，与生理盐水相比，d-安非他明显著缩短了平均苏醒时间（生理盐水：112.8±37.2分钟；d-安非他明：1.8±0.6分钟，p < 0.0001）。D1/D5多巴胺受体拮抗剂SCH-23390可消除这种唤醒效应。与生理盐水相比，氯胺酮后d-安非他明未显著加快苏醒时间（生理盐水：19.7±18.0 min； d-安非他明：20.3±16.5 min, p = 1.00）。前额叶皮层局部场电位记录显示，d-安非他明广泛降低频率<25 Hz的频谱功率，并恢复右美托咪定后的清醒模式。而d-安非他明在氯胺酮之后没有产生明显的光谱变化。服用右美托咪定和氯胺酮的女性昏迷持续时间明显更长。总之，右美托咪定后，d-安非他明能迅速恢复意识，而氯胺酮则不能。SCH-23390可抑制右美托咪定逆转，提示唤醒效应是由D1和/或D5受体介导的。这些发现表明d-安非他明可能在临床上作为右美托咪定的逆转剂有用。
D-amphetamine induces emergence from sevoflurane and propofol anesthesia in rats. Dexmedetomidine is an α2-adrenoreceptor agonist that is commonly used for procedural sedation, whereas ketamine is an anesthetic that acts primarily by inhibiting NMDA-type glutamate receptors. These drugs have different molecular mechanisms of action from propofol and volatile anesthetics that enhance inhibitory neurotransmission mediated by GABAA receptors. In this study, we tested the hypothesis that d-amphetamine accelerates recovery of consciousness after dexmedetomidine and ketamine. Sixteen rats (Eight males, eight females) were used in a randomized, blinded, crossover experimental design and all drugs were administered intravenously. Six additional rats with pre-implanted electrodes in the prefrontal cortex (PFC) were used to analyze changes in neurophysiology. After dexmedetomidine, d-amphetamine dramatically decreased mean time to emergence compared to saline (saline:112.8 ± 37.2 min; d-amphetamine:1.8 ± 0.6 min, p < 0.0001). This arousal effect was abolished by pre-administration of the D1/D5 dopamine receptor antagonist, SCH-23390. After ketamine, d-amphetamine did not significantly accelerate time to emergence compared to saline (saline:19.7 ± 18.0 min; d-amphetamine:20.3 ± 16.5 min, p = 1.00). Prefrontal cortex local field potential recordings revealed that d-amphetamine broadly decreased spectral power at frequencies <25 Hz and restored an awake-like pattern after dexmedetomidine. However, d-amphetamine did not produce significant spectral changes after ketamine. The duration of unconsciousness was significantly longer in females for both dexmedetomidine and ketamine. In conclusion, d-amphetamine rapidly restores consciousness following dexmedetomidine, but not ketamine. Dexmedetomidine reversal by d-amphetamine is inhibited by SCH-23390, suggesting that the arousal effect is mediated by D1 and/or D5 receptors. These findings suggest that d-amphetamine may be clinically useful as a reversal agent for dexmedetomidine.
登录
查看更多内容
影响因子：
8.8
作者：
Fong R;Wang L;Zacny JP;Khokhar S;Apfelbaum JL;Fox AP;Xie Z
通讯作者：
Xie Z
影响因子：
5.7
作者：
Kelz, Max B.;Garcia, Paul S.;Solt, Ken
通讯作者：
Solt, Ken
影响因子：
5
作者：
DIPAOLO, T;ROUILLARD, C;BEDARD, P
通讯作者：
BEDARD, P
DOI：
10.1007/bf03013235
发表时间：
1999-04-01
期刊：
CANADIAN JOURNAL OF ANAESTHESIA-JOURNAL CANADIEN D ANESTHESIE
影响因子：
--
作者：
Kubota, T;Anzawa, N;Matsuki, A
通讯作者：
Matsuki, A
影响因子：
3.3
作者：
Hiyoshi, T.;Kambe, D.;Chaki, S.
通讯作者：
Chaki, S.