Ketamine and Midazolam Neurotoxicity in the Rabbit

Malinovsky, Jean-Marc; Cozian, A.; Lepage, Jean-Yves; Mussini, Jean-Marie; Pinaud, M.; Souron, R

doi:10.1097/00000542-199107000-00015

Cited by 227 publications

(84 citation statements)

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“…The antinociceptive properties of midazolam after intrathecal administration have recently been reported in animals, 4-7 and its therapeutic effect evaluated in patients with chronic back pain, S,9 despite evidence of midazolam-induced neurotoxicity in one animal model. 10 The purpose of the present study was to examine the effect of intrathecal midazolam on isoflurane MAC in a dose-response fashion in isoflurane-anaesthetized, tracheotomized rats. Since the respiratory effects of intmthecal midazolam remain unknown, the apnoeic threshold after each intrathecal dose was also evaluated.…”

Section: Ce Travail Vise ~ D~terminer La Relation Dose-effet Du Midazmentioning

confidence: 99%

Intrathecal midazolam reduces isoflurane MAC and increases the apnoeic threshold in rats

et al. 1994

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Section: Ce Travail Vise ~ D~terminer La Relation Dose-effet Du Midazmentioning

confidence: 99%

Intrathecal midazolam reduces isoflurane MAC and increases the apnoeic threshold in rats

et al. 1994

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“…Recently midazolam has been shown to induce apoptosis in human Jurkat T-lymphoma cells that lack GABA A receptor (Stevens et al, 2011). In addition, animal studies using midazolam have shown rather contradictory neurotoxicity and apoptosis responses in sheep, rabbits, and rodents (Erdine et al, 1999;Johansen et al, 2004;Malinovsky et al, 1991;Schoeffler et al, 1991;Svensson et al, 1995;Yon et al, 2005;Young et al, 2005). Apoptosis induction is achieved through two main pathways, death receptor-dependent extrinsic or mitochondrial intrinsic.…”

Section: Introductionmentioning

confidence: 99%

Midazolam Induces Cellular Apoptosis in Human Cancer Cells and Inhibits Tumor Growth in Xenograft Mice

Mishra

Kang

Lee

et al. 2013

Molecules and Cells

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Midazolam is a widely used anesthetic of the benzodiazepine class that has shown cytotoxicity and apoptosisinducing activity in neuronal cells and lymphocytes. This study aims to evaluate the effect of midazolam on growth of K562 human leukemia cells and HT29 colon cancer cells. The in vivo effect of midazolam was investigated in BALB/ c-nu mice bearing K562 and HT29 cells human tumor xenografts. The results show that midazolam decreased the viability of K562 and HT29 cells by inducing apoptosis and S phase cell-cycle arrest in a concentration-dependent manner. Midazolam activated caspase-9, capspase-3 and PARP indicating induction of the mitochondrial intrinsic pathway of apoptosis. Midazolam lowered mitochondrial membrane potential and increased apoptotic DNA fragmentation. Midazolam showed reactive oxygen species (ROS) scavenging activity through inhibition of NADPH oxidase 2 (Nox2) enzyme activity in K562 cells. Midazolam caused inhibition of pERK1/2 signaling which led to inhibition of the anti-apoptotic proteins Bcl-X L and XIAP and phosphorylation activation of the pro-apoptotic protein Bid. Midazolam inhibited growth of HT29 tumors in xenograft mice. Collectively our results demonstrate that midazolam caused growth inhibition of cancer cells via activation of the mitochondrial intrinsic pathway of apoptosis and inhibited HT29 tumor growth in xenograft mice. The mechanism underlying these effects of midazolam might be suppression of ROS production leading to modulation of apoptosis and growth regulatory proteins. These findings present possible clinical implications of midazolam as an anesthetic to relieve pain during in vivo anticancer drug delivery and to enhance anticancer efficacy through its ROS-scavenging and pro-apoptotic properties.

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“…And later in 1991, Malinovsky et al demonstrated potential of neurotoxic effect of intrathecal administration of ketamine and midazolam in rabbits [43]. Midazolam-treated rabbits showed significant changes in both blood-brain barrier and light microscopy studies.…”

Section: Topics In Spinal Anaesthesiamentioning

confidence: 99%

Midazolam in Spinal Anesthesia — Intrathecal or Intravenous?

Zencirci¹

2014

Topics in Spinal Anaesthesia

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Ketamine and Midazolam Neurotoxicity in the Rabbit

Cited by 227 publications

References 0 publications

Intrathecal midazolam reduces isoflurane MAC and increases the apnoeic threshold in rats

Intrathecal midazolam reduces isoflurane MAC and increases the apnoeic threshold in rats

Midazolam Induces Cellular Apoptosis in Human Cancer Cells and Inhibits Tumor Growth in Xenograft Mice

Midazolam in Spinal Anesthesia — Intrathecal or Intravenous?

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