OBJECTIVETo study the psychedelic effects in healthy volunteers when given subanesthetic dose of ketamine.

METHODSThirteen male healthy volunteers aged 24-39 years were enrolled. All subjects received subanesthetic doses of ketamine using target control infusion. A stepwise series of target plasma concentrations (0, 100, 200, and 300 ng/ml) were maintained for 20 minutes each. Visual analogue scale (VAS) of mechanical pain by von Frey hair was evaluated, and then the volunteers completed a VAS rating of 13 symptom scales. Pictures were shown to them at the same time. Heart rate, mean blood pressure, and SpO2 were monitored throughout the infusion.

RESULTSDuring the process of analgesia, ketamine produced dose-related analgesic effects. With the increase of ketamine dose, some psychedelic effects became more obvious and the memory impairment became worse stepwisely.

CONCLUSIONTarget control infusion of subanesthetic doses of ketamine produce obvious psychedelic effects in healthy volunteers.

Adult ; Anesthetics, Dissociative ; administration & dosage ; adverse effects ; pharmacology ; Dose-Response Relationship, Drug ; Hallucinations ; chemically induced ; Humans ; Ketamine ; administration & dosage ; adverse effects ; pharmacology ; Male

OBJECTIVETo observe the effect of orexin-A on the recovery and cognitive function of aged rats after ketamine anesthesia.

METHODSFifty-five aged rats were divided randomly into control group, model control group, 1 nmol/L Orexin-A group, and 4 nmol/L Orexin-A group. In the latter 3 groups, the rats received an intraperitoneal injection of ketamine at 100 mg/kg, and normal saline was injected in the control group. Ten minutes after the injections, the rats received intraventricular injections of artificial cerebrospinal fluid (control and model control group) or of 10 microl 1 or 4 nmol/L Orexin-A as indicated. The behavioral changes of the rats were assessed by the duration of loss of righting reflex (LORR). Electroencephalogram (EEG) recordings were used to evaluate the changes in rat brain activity by comparison of the percent of sigma wave in EEG before and after the intraventricular injections. Morris water maze was used to test the learning and spatial localization abilities of the rats.

RESULTSKetamine resulted in obvious impairment of learning and memory abilities of the aged rats. Orexin-A at 4 nmol/L induced significant decrease in the duration of LORR and marked reduction of sigma activities in anesthetic rats (P<0.05), and obviously improved the learning and spatial localization abilities of the rats after anesthesia (P<0.05).

CONCLUSIONOrexin-A can promote the recovery and improve the cognitive function of aged rats after ketamine anesthesia.

Aging ; Anesthesia Recovery Period ; Anesthetics, Dissociative ; Animals ; Cognition ; drug effects ; Delayed Emergence from Anesthesia ; prevention & control ; Intracellular Signaling Peptides and Proteins ; pharmacology ; Ketamine ; Male ; Neuropeptides ; pharmacology ; Orexins ; Random Allocation ; Rats ; Rats, Sprague-Dawley

The effects of ketamine on transient outward potassium current (I(to)) of isolated human atrial myocytes were investigated to understand the mechanism of part of its effects by whole-cell patch-clamp. Atrial myocytes were enzymatically isolated from specimens of human atrial appendage obtained from patients under going cardiac valve displacing. Ito is recorded in voltage-clamp modes using the patch-clamp technique at room temperature. Currents signals were recorded by an Axopatch 200B amplifier with the Digidata 1322A-pClamp 9.0 data acquisition system. Ketamine decreased I(to) of human atrial myocytes in a dose-dependent manner. The current-voltage curve was significantly lowered, 30, 100, 300, and 1000 micromol x L(-1) ketamine decreased respectively I(to) current density about (13.62 +/- 0.04)%, (38.92 +/- 0.05)%, (72.24 +/- 0.10)% and (83.84 +/- 0.05)% at the potential of 50 mV, with an IC50 of 121 micromol x L(-1). The I(to) activation curve, inactivation curve and the recovery curve were not altered by ketamine. So, ketamine concentration-dependently decreased I(to) of human atrial myocytes.
Adolescent ; Adult ; Aged ; Anesthetics, Dissociative ; administration & dosage ; pharmacology ; Dose-Response Relationship, Drug ; Female ; Heart Atria ; cytology ; Humans ; Ketamine ; administration & dosage ; pharmacology ; Male ; Middle Aged ; Myocytes, Cardiac ; cytology ; drug effects ; physiology ; Patch-Clamp Techniques ; Potassium Channels ; drug effects ; Young Adult

Ketamine (KTM), a N-methyl-D-aspartate (NMDA) receptor antagonist, was found to has an anti-inflammatory effect, but some patients suffered from exacerbated pro-inflammatory reactions after anesthesia with KTM. The present study was aimed to examine the underlying mechanism of pro-inflammatory effects of KTM. In this study, RAW264.7 cells were exposed to KTM and NMDA alone or combined for 30 min before lipopolysaccharide (LPS) stimulation. The expression levels of IL-6 and TNF-α were detected by RT-PCR and ELISA, and those of NMDA receptors by RT-PCR in RAW264.7 cells. Additionally, the TLR4 expression was determined by RT-PCR and flow cytometry, respectively. The results showed that in RAW264.7 cells, KTM alone promoted the TLR4 expression, but did not increase the expression of IL-6 or TNF-α. In the presence of LPS, KTM caused a significantly higher expression of IL-6 and TNF-α than LPS alone. NMDA could neither alter the IL-6 and TNF-α mRNA expression, nor reverse the enhanced expression of IL-6 and TNF-α mRNA by KTM in LPS-challenged cells. After TLR4-siRNA transfection, RAW264.7 cells pretreated with KTM no longer promoted the IL-6 and TNF-α expression in the presence of LPS. In conclusion, KTM accelerated LPS-induced inflammation in RAW264.7 cells by promoting TLR4 expression, independent of NMDA receptor.
Anesthetics, Dissociative ; pharmacology ; Animals ; Cell Survival ; drug effects ; Gene Expression Regulation ; Inflammation Mediators ; pharmacology ; Interleukin-6 ; genetics ; Ketamine ; pharmacology ; Lipopolysaccharides ; pharmacology ; Macrophages ; drug effects ; metabolism ; Male ; Mice ; N-Methylaspartate ; pharmacology ; RAW 264.7 Cells ; Signal Transduction ; drug effects ; Toll-Like Receptor 4 ; genetics ; metabolism ; Tumor Necrosis Factor-alpha ; genetics

Apoptosis is a programmed, physiologic mode of cell death that plays an important role in tissue homeostasis. As for the central nervous system, ischemic insults can induce pathophysiologic cascade of apoptosis in neurophils. Impairment of astroctye functions during brain ischemia can critically influence neuron survival by neuronglia interactions. We aimed to elucidate the protective effect of ketamine on apoptosis by energy deprivation in astrocytes. Ischemic insults was induced with iodoacetate/ carbonylcyanide mchlorophenylhydrazone (IAA/CCCP) 1.5 mM/ 20 micrometer or 150 micrometer/2 micrometer for 1 hr in the HTB-15 and CRL-1690 astrocytoma cells. Then these cells were reperfused with normal media or ketamine (0.1 mM) containing media for 1 hr or 24 hr. FITC-annexin-V staining and propidium iodide binding were determined by using flow cytometry. Cell size and granularity were measured by forward and side light scattering properties of flow cytometry system, respectively. An addition of keta-mine during reperfusion increased the proportion of viable cells. Ketamine alleviated cell shrinkage and increased granularity during the early period, and ameliorated cell swelling during the late reperfusion period. Ketamine may have a valuable effect on amelioration of early and late apoptosis in the astrocytoma cells, even though the exact mechanism remains to be verified.
Anesthetics, Dissociative/*pharmacology ; Annexin A5/pharmacology ; Apoptosis ; Astrocytes/metabolism ; Astrocytoma/*drug therapy/pathology ; Brain/pathology ; Carbonyl Cyanide m-Chlorophenyl Hydrazone/pharmacology ; Cell Line, Tumor ; Cell Size ; Cell Survival ; Central Nervous System/drug effects/pathology ; Enzyme Inhibitors/pharmacology ; Flow Cytometry/*methods ; Humans ; Indicators and Reagents/pharmacology ; Iodoacetates/pharmacology ; Ischemia/pathology ; Ketamine/metabolism/*pharmacology ; Light ; Neurons/metabolism/pathology ; Neutrophils/metabolism ; Perfusion ; Propidium/pharmacology ; Scattering, Radiation ; Time Factors ; Uncoupling Agents/pharmacology

OBJECTIVE: To explore the effect of ketamine on adrenal pheochromocytoma (PC12) cell proliferation inhibition and induction of apoptosis and its mechanism. METHODS: PC12 cells of rats were models for dopaminergic neuron. PC12 cells were cultured with ketamine at concentrations of 0.9, 1.2, 1.5, 1.8 and 2.1 mmol/L, respectively. The cell viability was measured by MTT method after incubation at 12, 24, 48 and 72h. Hoechst stain was used to observe the morphological changes of apoptosis. PC12 cells cultured after 48 h with different concentrations of ketamine were selected to detect apoptotic rate using flow cytometry and detect the expression of bax and bcl-2 proteins using Western blotting. RESULTS: For different concentrations of ketamine, vitality of PC12 cells significantly decreased with increase of the incubation time. Apoptosis was obviously observed using Hoechst staining. Flow cytometry showed that apoptosis rates significantly increased with increasing ketamine concentrations. CONCLUSION Ketamine can inhibit the proliferation of PC12 cell by inducing apoptosis of the PC12 cell in a concentrations-dependent manner. The underlying mechanism may be related to promoting the expression of bax and inhibiting the expression of bcl-2 in the cells.
Anesthetics, Dissociative/pharmacology* ; Animals ; Apoptosis/drug effects* ; Blotting, Western ; Cell Proliferation/drug effects* ; Dose-Response Relationship, Drug ; Flow Cytometry ; Gene Expression Regulation/drug effects* ; Ketamine/pharmacology* ; PC12 Cells ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Rats ; Time Factors ; bcl-2-Associated X Protein/metabolism*