The Efficacy and Safety of the Novel Peripheral Analgesic Isovaline as an Adjuvant to Propofol for General Anesthesia and Conscious Sedation

Whitehead, Ryan A.; Schwarz, Stephan; Asiri, Yahya I.; Fung, Timothy; Puil, E.; MacLeod, Bernard A.

doi:10.1213/ane.0000000000000996

Cited by 9 publications

(3 citation statements)

References 29 publications

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“…In a previous animal study, hypnosis was defined as the inability of a supine mouse to turn upright from sternal recumbency (loss of righting reflex) and the absence of response to light touch (gentle pinch at the hind paw). 10 Since the animals' heads were in a head restraint in our study, we were only able to define hypnosis by the absence of a response to light touch. The respiratory and circulatory responses during administration of propofol were not monitored during the experiment, although all mice recovered from anesthesia.…”

Section: Resultsmentioning

confidence: 99%

The Effects of Propofol on Neural Responses in the Mouse Primary Auditory Cortex

Wang

et al. 2020

Journal of Neurosurgical Anesthesiology

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Objective: Two-photon laser-scanning microscopy allows for the monitoring of all brain neurons with single-cell and single-action potential accuracy. This study aimed to investigate the neural responses of the primary auditory cortex to sound stimuli in awake and propofol-anesthetized mice using 2-photon laserscanning microscopy.Methods: Twelve healthy adult male C57BL/6 mice were used in the present study. In each mouse, the scalp was removed over the entire dorsal skull, and the right primary auditory cortex (A1) located. The test stimulus, used in the awake and propofolinduced anesthetic state, was a group of tones with a random combination of 3 sound intensities and 8 sound frequencies. The calcium indicator GCaMP6s was virally expressed in cortical neurons and neuronal activity was recorded using 2-photon imaging.Results: Calcium responses to sound stimuli in two thirds of the neuronal population of the A1 layer were significantly inhibited by propofol anesthesia. In a single neuron, the calcium responses were also inhibited by propofol anesthesia. In the waking state, △F/F (where F is the time series of fluorescence intensity) of all single neurons was significantly higher than that in the propofolinduced anesthetic state (n = 669, P < 0.001). Finally, in one example session and averaged across different fields of views (n = 6 sessions), the response events to sound stimuli were also inhibited by propofol anesthesia. Conclusion:Anesthetic doses of propofol inhibited calcium transients and neuronal activity in the primary auditory cortex of mice.

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Section: Resultsmentioning

confidence: 99%

The Effects of Propofol on Neural Responses in the Mouse Primary Auditory Cortex

Wang

et al. 2020

Journal of Neurosurgical Anesthesiology

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“…The up and down procedure was used in the loss of righting reflex (LRR) assay to determine ED 50 of sedation [20]. The LRR for more than 10 s was regarded as positive for sedation; otherwise, the observation was regarded as negative [21].…”

Section: Righting Reflex Testmentioning

confidence: 99%

Nanoformulation of Premixing Propofol Lipid Emulsion and Fentanyl Citrate and Their Effects on Acute Toxicity, Sedation, and Analgesia

Gao

Sha

Liu

et al. 2016

Journal of Nanomaterials

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To illustrate the effects of premixing propofol lipid emulsion (PLE) and fentanyl citrate (FC) on acute toxicity, sedation, and analgesia, sixty female mice were randomly assigned to individual and premixed groups. The median lethal dose (LD50), median effective dose (ED50) of loss of righting reflex, and ED50of tail flick test in both groups were determined using the up and down procedure (FC : PLE = 1 μg : 2 mg). PLE was immediately administered to the mice from the individual group via the tail vein after injecting FC. By contrast, FC was mixed with PLE before injection from the premixed group. No significant differences in LD50, histopathological examination, and ED50sedation value were found between the groups. However, ED50of analgesia in the premixed group decreased to half of that in the individual group. Transmission electron microscopic observation revealed ~10 nm fusiform particles at the juncture of 200–300 nm particles in the mixture of PLE and FC compared with the single PLE and its mixture with saline, which may be attributed to the structure of FC. In conclusion, premixing PLE and FC enhanced synergic analgesia twofold but did not influence toxicity and sedation compared with individual injections.

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“…Our laboratory has focused on an unusual analgesic prototype, isovaline, a small amino acid that activates peripheral GABA B and group II metabotropic glutamate receptors to produce antinociception. Isovaline has no apparent adverse effects following systemic or central administration in various murine pain models (Lim & Lee, ; MacLeod et al., ; Whitehead et al., ; Asseri, Puil, Schwarz, & MacLeod, ; Whitehead et al., ). Furthermore, structure–activity relationship (SAR) studies of isovaline revealed that the amino acid, 1‐amino‐1‐cyclobutanecarboxylic acid (ACBC), produces antinociceptive effects in the formalin foot assay (Fung et al., ).…”

Section: Introductionmentioning

confidence: 99%

Antinociception by intrathecal delivery of the novel non‐opioid 1‐amino‐1‐cyclobutanecarboxylic acid

Fung

Asiri

Taheri³

et al. 2018

European Journal of Pain

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The Efficacy and Safety of the Novel Peripheral Analgesic Isovaline as an Adjuvant to Propofol for General Anesthesia and Conscious Sedation

Cited by 9 publications

References 29 publications

The Effects of Propofol on Neural Responses in the Mouse Primary Auditory Cortex

The Effects of Propofol on Neural Responses in the Mouse Primary Auditory Cortex

Nanoformulation of Premixing Propofol Lipid Emulsion and Fentanyl Citrate and Their Effects on Acute Toxicity, Sedation, and Analgesia

Antinociception by intrathecal delivery of the novel non‐opioid 1‐amino‐1‐cyclobutanecarboxylic acid

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