Methamphetamine (METH) is widely abused in worldwide. METH use could damage the dopaminergic system and induce neurotoxicity via oxidative stress and mitochondrial dysfunction. Propofol, a sedative-hypnotic agent, is known for its antioxidant properties. In this study, we used propofol for attenuating of METH-induced neurotoxicity in rats.

Propofol is an anesthetic commonly used to provide sedation or to induce and maintain an anesthetic stated. However, there are reports which indicate propofol may cause psychological dependence or be abused. In the present study, we used various behavioral tests including climbing test, jumping test, conditioned place preference, and self-administration test to assess the dependence potential and abuse liability of propofol compared to a positive control (methamphetamine) or a negative control (saline or intralipid). Among the tests, the conditioned place preference test was conducted with a biased method, and the selfadministration test was performed under a fixed ratio (FR) 1 schedule, 1 h per session. No difference was found in the climbing test and jumping test, but propofol (30 mg/kg, i.p.) increased the rewarding effect in the conditioned place preference test, and it showed a positive reinforcing effect compared to the vehicle. These results indicate that propofol tends to show psychological dependence rather than physical dependence, and it seems not to be related with dopaminergic system.

Vasopressors are frequently used to increase blood pressure in order to ensure sufficient cerebral perfusion and oxygenation (CPO) during hypotensive periods in anaesthetized patients. Efficacy depends both on the vasopressor and anaesthetic protocol used. Propofol-remifentanil total intravenous anaesthesia (TIVA) is common in human anaesthesia, and dexmedetomidine is increasingly used as adjuvant to facilitate better haemodynamic stability and analgesia. Little is known of its interaction with vasopressors and subsequent effects on CPO. This study investigates the CPO response to infusions of norepinephrine and phenylephrine in piglets during propofol-remifentanil and propofol-remifentanil-dexmedetomidine anaesthesia. Sixteen healthy female piglets (25-34 kg) were randomly allocated into a two-arm parallel group design with either normal blood pressure (NBP) or induced low blood pressure (LBP). Anaesthesia was induced with propofol without premedication and maintained with propofol-remifentanil TIVA, and finally supplemented with continuous infusion of dexmedetomidine. Norepinephrine and phenylephrine were infused in consecutive intervention periods before and after addition of dexmedetomidine. Cerebral perfusion measured by laser speckle contrast imaging was related to cerebral oxygenation as measured by an intracerebral Licox probe (partial pressure of oxygen) and transcranial near infrared spectroscopy technology (NIRS) (cerebral oxygen saturation).

Propofol (2,6-diisopropylphenol) is the most commonly used intravenous agent for induction of anesthesia. It is also used for maintenance of anesthesia and sedation in both Intensive Care Units and outpatient procedural settings. Its success in the clinical setting has been a result of its rapid onset, short duration of action, and minimal side effects despite disadvantages associated with its oil emulsion formulation. Early attempts to alter the standard emulsion or to develop new formulations with cyclodextrins and micelles to resolve issues with pain upon injection, the need for antimicrobial agents, and possible hyperlipidemia have mostly failed. With these challenges in the foreground, attention has now shifted to the use of more prodrugs and exogenous alternatives, the success of which is yet to be determined. These new agents must offer significant clinical advantages over the well-entrenched, generic propofol oil emulsion to justify higher costs and to be well received in the increasingly cost-conscious healthcare marketplace.

Although the loop electrosurgical excision procedure (LEEP) is a brief procedure, it can cause severe pain and discomfort to patients in the absence of adequate sedation. An admixture of ketamine with propofol (ketofol), may reduce patient movement due to insufficient sedation while providing hemodynamic and respiratory stability. This study evaluated the ability of two ratios of a propofol-ketamine combination, compared with propofol alone, to reduce patient movement during procedural sedation for LEEPs.

Tracheal intubation without muscle relaxants is usually performed with remifentanil and propofol or sevoflurane. Remifentanil 1.0 to 4.0 μg·kg(-1) and propofol 2.0-3.0 mg·kg(-1) or sevoflurane up to 8.0 Vol% provide acceptable, i.e. excellent or good intubating conditions. We hypothesized that sevoflurane 1.0 MAC would provide acceptable intubating conditions when combined with propofol and remifentanil.

Propofol (2, 6-diisopropylphenol) is an intravenous sedative-hypnotic agent administered to induce and maintain anesthesia. It has been recently revealed that propofol has anticancer properties including direct and indirect suppression of the viability and proliferation of cancer cells by promoting apoptosis in some cancer cell lines.

Despite their frequent use across many clinical settings, general anesthetics are medications with lethal side effects and no reversal agents. A fluorinated analogue of propofol has previously been shown to antagonize propofol anesthesia in tadpoles and zebrafish, but little further investigation of this class of molecules as anesthetic antagonists has been conducted. A 13-member library of alkyl-fluorobenzene derivatives was tested in an established behavioral model of anesthesia in zebrafish at 5 days post fertilization. These compounds were examined for their ability to antagonize propofol and two volatile anesthetics, as well as their binding to the anesthetic-binding model protein apoferritin. The two compounds demonstrating highest antagonistic potency were found to bind apoferritin in a manner similar to propofol. Selected compounds did not show antagonism of volatile anesthetics, indicating some selectivity of this antagonism. Similarities in structure and binding to apoferritin as well as a Schild analysis are suggestive of competitive antagonism, but like the anesthetics, the potential mechanism(s) of these antagonists will require further mechanistic investigation.

Background: Propofol injection pain, despite various interventions, still occurs during the anesthesia induction and causes intense discomfort and anxiety in patients. This study aimed to explore the effect of intravenous dexmedetomidine on propofol injection pain prior to anesthesia induction with propofol at 4°C. Methods: A total of 251 patients (American Society of Anesthesiologists I-II) who underwent oral and maxillofacial surgery were randomly assigned to a combination group (n = 63), lidocaine group (n = 62), dexmedetomidine group (n = 63), and placebo-control group (n = 63); they received 0.5 ug/kg dexmedetomidine prior to anesthesia induction with propofol at 4°C, 40 mg lidocaine, 0.5 ug/kg dexmedetomidine prior to anesthesia induction, and normal saline, respectively. Incidence of pain, pain intensity, and reaction to the pain stimulus were evaluated by using verbal categorial scoring (VCS), a numerical rating scale (NRS), and the Surgical Pleth Index (SPI), respectively. In addition, hemodynamic parameters such as heart rate (HR) and mean arterial pressure (MAP) were also measured. The VCS and NRS were evaluated at 5 s after propofol injection. In addition, SPI, HR, and MAP were evaluated at three time points (before anesthesia induction and 5 and 30 s after propofol injection). Results: The incidence of pain in the combination group (51%) was significantly lower than that in the lidocaine group (71%), dexmedetomidine group (67%), or placebo-control group (94%) (p < 0.001). VCS and NRS scores in the combination group were also lower compared with the other three groups (p < 0.001), with no statistically significant differences between the lidocaine group and dexmedetomidine group (p > 0.05). The SPI of the combination group decreased significantly in comparison with the other three groups at 5 s after propofol injection (F = 96.23, p < 0.001) and 30 s after propofol injection (F = 4.46, p = 0.005). Further comparisons between HR and MAP revealed no significant differences across the groups (p > 0.05). Conclusion: Because of the sedative nature of dexmedetomidine and analgesic effect of low temperature, this study showed that intravenous dexmedetomidine prior to anesthesia induction with propofol at 4°C is highly effective in attenuating the incidence and severity of pain during injection compared with lidocaine (40 mg), dexmedetomidine 0.5 ug/kg) and placebo. This approach was not associated with any anesthesia complications. Clinical Trial Registration: ClinicalTrials.gov, identifier: ChiCTR-2000034663.

To compare the effects of intravenous infusion of ketamine and propofol anesthesia in children undergoing strabismus surgery.

Background: Propofol is a widely used anesthetic. Whether propofol inhibits androgen production by rat Leydig cells and the underlying mechanism remains unclear. The objective of the current study was to examine the effects of propofol exposure to rat primary immature Leydig cells and to define propofol-induced inhibition of steroidogenic enzymes in both rat and human testes in vitro. Methods: Immature Leydig cells were purified from 35-day-old male Sprague-Dawley rats and were exposed to propofol for 3 h. The androgen production by Leydig cells under basal, luteinizing hormone, 8bromo-cAMP, and steroid-substrate stimulated conditions and gene expression of Leydig cells after exposure to propofol were measured. Immature Leydig cells were treated with propofol for 3 h and switched to propofol-free medium for additional 3 and 9 h to test whether propofol-induced inhibition is reversible. 3H-Steroids were used to evaluate the direct action of propofol on cytochrome P450 cholesterol side chain cleavage (CYP11A1), 3β-hydroxysteroid dehydrogenase (HSD3B), cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17A1), and 17β-hydroxysteroid dehydrogenase 3 (HSD17B3) activities in rat and human testes in vitro. Results: Propofol significantly lowered luteinizing hormone and 8bromo-cAMP stimulated androgen production by Leydig cells after 3-h exposure. Further investigation showed that propofol down-regulated the expression of Cyp11a1 and Cyp17a1 and their proteins at 5 and 50 µM, although it up-regulated Lhcgr expression at 50 µM. Propofol significantly suppressed phosphorylation of ERK1/2 and induced ROS production in immature Leydig cells at 5 and 50 µM. Propofol significantly induced apoptosis of immature Leydig cells at 50 µM. Propofol specifically inhibited rat and human testis HSD3B activities in vitro. The half maximal inhibitory concentrations of propofol for rat and human HSD3B enzymes were 1.011 ± 0.065 and 3.498 ± 0.067 µM, respectively. The mode of action of propofol of inhibiting HSD3B was competitive when pregnenolone was added. At 50 µM, propofol did not directly inhibit rat and human testis CYP11A1, CYP17A1, and HSD17B3 activities in vitro. Conclusion: Propofol inhibits androgen production via both directly inhibiting HSD3B activity and down-regulating Cyp11a1 and Cyp17a1 expression in Leydig cells. Suppression of steroidogenic enzymes is presumably associated with the lower production of androgen by Leydig cells after propofol treatment. However, propofol-induced inhibition on androgen production is reversible.

Propofol is an ultra-short acting anesthetic agent. The information on the pharmacological and toxicological effects of propofol in the chicken is rather limited. This study examines the toxicity and pharmaco-behavioral effects of propofol given intraperitoneally in 7-10 day-old chicks. The median effective doses of propofol for the induction of sedation, analgesia to electric stimulation and sleep in the chicks were 1.82, 2.21 and 5.71 mg/kg, respectively. The 24-h median lethal dose of propofol in chicks was 57.22 mg/kg. The therapeutic indices of propofol for sedation, analgesia and sleep were 31.4, 25.9 and 10, respectively. Propofol at 0.5 and 1 mg/kg reduced the locomotor activity and increased the duration of tonic immobility in chicks. Propofol at 2 and 4 mg/kg caused analgesia to electric stimulation as well as analgesia and anti-inflammatory responses against formalin test in chicks. Propofol at 5, 10 and 20 mg/kg induced sleep in chicks for 8.4 to 25 min. Physostigmine shortened the sleep duration of propofol. Data suggest that propofol induces anti-inflammatory action and central nervous system depression in chicks resulting in sedation, analgesia and anesthesia with wide safety margin. These effects could form the basis of further pharmacological and toxicological studies on propofol in the young chick model, and the drug could be safely applied clinically in the chicken.

Exhaled propofol concentrations correlate with propofol concentrations in adult human blood and the brain tissue of rats, as well as with electroencephalography (EEG) based indices of anesthetic depth. The pharmacokinetics of propofol are however different in children compared to adults. The value of exhaled propofol measurements in pediatric anesthesia has not yet been investigated. Breathing system filters and breathing circuits can also interfere with the measurements. In this study, we investigated correlations between exhaled propofol (exP) concentrations and the Narkotrend Index (NI) as well as calculated propofol plasma concentrations.

The aim of the present study was to verify whether propofol impaired learning and memory through the interplay of N-methyl-D-aspartate (NMDA) receptor with brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) signaling pathway.

How general anesthesia interferes with sensory processing to cause amnesia remains unclear. Here, we show that activation of a learning-associated immediate early gene in rat olfactory cortices is uninterrupted by propofol, an intravenous general anesthetic with putative actions on the inhibitory GABAA receptors. Once learned under anesthesia, a novel odor can no longer re-activate the same high-level transcription programming during subsequent conscious relearning. Behavioral tests indicate that the animals' ability to consciously relearn a pure odorant, first experienced under general anesthesia, is indeed compromised. In contrast, when a mixture of two novel odorants is first experienced under anesthesia and then relearned consciously in pairs with one of the components, the animals show a deficit in relearning only the component but not the mixture. Our results reveal a previously unknown mechanism of unconscious memory due to irreplaceable neuronal commitment under general anesthesia and support the notion that general anesthesia acts at stages beyond cellular coding to disrupt sensory integration for higher-order association.

Propofol has emerged as an induction agent of choice over the past two decades due to its quick, smooth induction and rapid recovery. The main concern for an anesthesiologist is the hemodynamic instability caused by the standard induction dose of propofol (2-3 mg/kg).

Although propofol is a widely used intravenous general anaesthetic, many studies report its toxic potential, particularly on the developing central nervous system. We investigated its action on hypoglossal motoneurons (HMs) that control two critical functions in neonates, namely tongue muscle activity and airway patency. Thus, clinically relevant concentrations of propofol (1 and 5μM) were applied (4h) to neonatal rat brainstem slices to evaluate the expression of apoptosis-inducing factor (AIF) as biomarker of toxicity. This anaesthetic strongly increased AIF in the cytoplasm and the nucleus, without early loss of HMs. Electrophysiological recordings from HMs showed that propofol (5μM) enhanced GABA- and glycine-evoked current amplitude and lengthened GABAergic current decay time. Propofol also depressed NMDA receptor-mediated responses without affecting AMPA receptors. Since GABA and glycine depolarize neonatal HMs, we propose that the damaging action by propofol on these motoneurons might arise from the facilitated action of these transmitters with subsequent cytoplasmic Ca2+ overload. This phenomenon, in turn, may trigger cell death mechanisms manifested as increased expression of AIF and its translocation into the nucleus. Since propofol is also employed for induction and maintenance of paediatric surgery, caution is needed because its potential neurotoxicity might negatively impact neurodevelopment.

Despite the extensive use of propofol in general anesthetic procedures, the effects of propofol on glial cell were not completely understood. In lipopolysaccharide (LPS)-stimulated rat primary astrocytes and BV2 microglial cell lines, co-treatment of propofol synergistically induced inflammatory activation as evidenced by the increased production of NO, ROS and expression of iNOS, MMP-9 and several cytokines. Propofol augmented the activation of JNK and p38 MAPKs induced by LPS and the synergistic activation of glial cells by propofol was prevented by pretreatment of JNK and p38 inhibitors. When we treated BV2 cell culture supernatants treated with LPS plus propofol on cultured rat primary neuron, it induced a significant neuronal cell death. The results suggest that the repeated use of propofol in immunologically challenged situation may induce glial activation in brain.

Propofol is a widely used general anesthetic, yet the understanding of its cellular effects is fragmentary. General anesthetics are not as innocuous as once believed and have a wide range of molecular targets that include kinesin motors. Propofol, ketamine, and etomidate reduce the distances that Kinesin-1 KIF5 and Kinesin-2 KIF3 travel along microtubules in vitro. These transport kinesins are highly expressed in the CNS, and their dysfunction leads to a range of human pathologies including neurodevelopmental and neurodegenerative diseases. While in vitro data suggest that general anesthetics may disrupt kinesin transport in neurons, this hypothesis remains untested. Here we find that propofol treatment of hippocampal neurons decreased vesicle transport mediated by Kinesin-1 KIF5 and Kinesin-3 KIF1A ∼25-60%. Propofol treatment delayed delivery of the KIF5 cargo NgCAM to the distal axon. Because KIF1A participates in axonal transport of presynaptic vesicles, we tested whether prolonged propofol treatment affects synaptic vesicle fusion mediated by VAMP2. The data show that propofol-induced transport delay causes a significant decrease in vesicle fusion in distal axons. These results are the first to link a propofol-induced delay in neuronal trafficking to a decrease in axonal vesicle fusion, which may alter physiological function during and after anesthesia.

Several drug combinations have been tried in patients with acyanotic congenital heart disease (ACHD) undergoing transcatheter device closure in the cardiac catheterisation laboratory (CCL). Adequate sedation, analgesia, akinesia, cardiorespiratory stability, and prompt recovery are key requirements. Ketamine with propofol is used for this purpose. Dexmedetomidine carries a shorter recovery time. This study compared dexmedetomidine-propofol (DP) with ketamine-propofol (KP) in patients in the CCL.