Effects of tiletamine on the adenosine monophosphate-activated protein kinase signaling pathway in the rat central nervous system

Su, Li-Xue; Shi, Xing-Xing; Yang, Peng; Chen, Hao; Li, Xin; Fan, Honggang; Wang, Hongbin

doi:10.1016/j.rvsc.2017.03.011

Cited by 4 publications

(5 citation statements)

References 31 publications

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“…The doses of KET used in the present research were chosen based on our previous studies (Potasiewicz et al 2017 ; Salat et al 2015c ) and available literature data (Eskelund et al 2017 ; Koike et al 2011 ; Zhu et al 2017 ). Since there is a limited amount of data regarding effective doses of TIL in rodents (Gargiulo et al 2012 ; Su et al 2017 ), we conducted preliminary dose-response studies (data not shown) to establish the starting dose of TIL (5 mg/kg in mice and 0.5 mg/kg in rats).…”

Section: Methodsmentioning

confidence: 99%

Comparison of the Psychopharmacological Effects of Tiletamine and Ketamine in Rodents

et al. 2017

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The glutamate N-methyl-d-aspartate (NMDA) receptor antagonist ketamine (KET) produces rapid and sustained antidepressant effects in patients. Tiletamine (TIL; 2-ethylamino-2-thiophen-2-yl-cyclohexan-1-one) is another uncompetitive NMDA receptor antagonist, used in a medical (veterinary) setting as an anesthetic tranquilizer. Here, we compared the behavioral actions of KET and TIL in a variety of tests, focusing on antidepressant-like and dissociative-like effects in mice and rats. The minimum effective doses of KET and TIL were 10 mg/kg to reduce mouse forced swim test immobility and 15 mg/kg to reduce marble-burying behavior. However, at similar doses, both compounds diminished locomotor activity and disturbed learning processes in the mouse passive avoidance test and the rat novel object recognition test. KET and TIL also reduced social behavior and accompanying 50-kHz “happy” ultrasonic vocalizations (USVs) in rats. TIL (5–15 mg/kg) displayed additional anxiolytic-like effects in the four-plate test. Neither KET nor TIL affected pain response in the hot plate test. Examination of the “side effects” revealed that only at the highest doses investigated did both compounds produce motor deficits in the rotarod test in mice. While KET produced behavioral effects at doses comparable between species, in the rats, TIL was ~10 times more potent than in the mice. In summary, antidepressant-like properties of both KET and TIL are similar, as are their adverse effect liabilities. We suggest that TIL could be an alternative to KET as an antidepressant with an additional anxiolytic-like profile.

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Section: Methodsmentioning

confidence: 99%

Comparison of the Psychopharmacological Effects of Tiletamine and Ketamine in Rodents

et al. 2017

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“…The AMPK signaling pathway (Yang, Guo, et al, 2021; Yang, Wang, et al, 2021), NF‐kB signaling pathway (El‐Kashef & Serrya, 2019), P53 signaling pathway (Yuan et al, 2020), and Trka receptor signaling pathway (Li et al, 2013) can up‐regulate S1PR1, inhibit inflammation, and reduce apoptosis, and are thus closely related to the liver protection. The AMPK signaling pathway (Su et al, 2017), dopaminergic synapse (Esposito et al, 1986; Taylor et al, 2019), and TGF‐beta signaling pathway (Lantero et al, 2014) are involved in the regulation of the endogenous opioid system through presynaptic and postsynaptic mechanisms. They inhibit the response of nociceptors and are important for mediating analgesia.…”

Section: Resultsmentioning

confidence: 99%

“…The AMPK signaling pathway (Su et al, 2017), dopaminergic synapse (Esposito et al, 1986;Taylor et al, 2019), and TGF-beta signaling pathway (Lantero et al, 2014) are involved in the regulation of the endogenous opioid system through presynaptic and postsynaptic mechanisms. They inhibit the response of nociceptors and are important for mediating analgesia.…”

Section: The Relationship Of Different Metabolites and Bioactivitiesmentioning

confidence: 99%

Identification of ginsenoside metabolites in plasma related to different bioactivities of Panax notoginseng and Panax ginseng

Dong

et al. 2022

Biomedical Chromatography

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Although the chemical components of Panax notoginseng (PN) and Panax ginseng (PG) are similar, their bioactivities are different. In this study, the differential bioactivities of PN and PG were used as the research object. First, the different metabolites in the plasma after oral administration of PN and PG were analyzed using a UPLC‐Q/TOF‐MS‐based metabolomics approach. Afterward, the metabolite‐target‐ pathway network of PN and PG was constructed, and thus the pathways related to different bioactivities were analyzed. As a result, 7 different metabolites were identified in PN group, and 10 different metabolites were identified in the PG group. In the PN group, the metabolite N1 was related to hemostasis, N1 and N3 were related to inhibiting the nerve center, antihypertensive, and abirritation. The metabolites N1, N3, N4, N5, and N6 were related to liver protection. The results showed that the metabolites G1, G2, G3, G5, and G6 in PG group were related to heart protection, and G1, G2, G6, and G9 were related to increased blood pressure. There were 13 signaling pathways related to different biological activities of PN (8 pathways) and PG (5 pathways). These pathways further clarified the mechanism of action that caused the different bioactivities between PN and PG. In summary, metabolomics combined with network pharmacology could be helpful to clarify the material basis of different bioactivities between PN and PG, promoting the research on PN and PG.

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Section: Nervous Systemmentioning

confidence: 99%

“…In the study conducted by Li-Xue Su et al tiletamine has been shown to reduce eIF4E-binding protein 1 (4EBP1) mRNA levels in the brain in rats (Su et al 2017). This information suggests that the anaesthetic may reduce neuronal activity to induce sedation by decreasing expression of the eIF4E-binding protein 1 (4EBP1) gene (Su et al 2017). The effect of tiletamine on the expression of liver kinase B1 (LKB1), activated AMPK (AMPKα), and 4EBP1 may partly underline the pharmacological action of the drug (Su et al 2017).…”

Section: Nervous Systemmentioning

confidence: 99%

Polish Journal of Veterinary Sciences

Kucharski

Kiełbowicz

2021

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This article is an attempt to gather available literature regarding the use of tiletamine and zolazepam combination in anaesthesia in dogs and cats. Although tiletamine and zolazepam mixture has been known in veterinary practice for a long time, the increased interest in these drugs has been observed only recently. Tiletamine, similarly to ketamine, is a drug which belongs to the phencyclidine group. Ketamine has considerable popularity in veterinary practice what suggests that other dissociative anaesthetic drugs, such as tiletamine, could also prove effective in cats' and dogs' anaesthetic care. Zolazepam is a widely used benzodiazepine known for its muscle relaxant and anticonvulsant properties. While conducting an electronic search for articles regarding the use of tiletamine-zolazepam combination in dogs and cats, it has been discovered that the literature on the subject (tiletamine-zolazepam combination in dogs and cats) is quite scarce. Very few articles were published after 2010. Databases used were: Google Scholar, Scopus, PubMed. Most of the adverse effects, including those affecting the cardiovascular, nervous, and respiratory systems, were strictly dose-dependent. Tiletamine-zolazepam combination can be safely used as a premedication agent, induction for inhalation anaesthesia, or an independent anaesthetic for short procedures. Contraindications using tiletamine-zolazepam mixture include central nervous system (CNS) diseases such as epilepsy and seizures, head trauma, penetrative eye trauma, cardiovascular abnormalities (hypertrophy cardiomyopathy in cats, arrythmias or conditions where increase of heart rate is inadvisable), hyperthyroidism, pancreatic deficiencies or kidney failure.

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Effects of tiletamine on the adenosine monophosphate-activated protein kinase signaling pathway in the rat central nervous system

Cited by 4 publications

References 31 publications

Comparison of the Psychopharmacological Effects of Tiletamine and Ketamine in Rodents

Comparison of the Psychopharmacological Effects of Tiletamine and Ketamine in Rodents

Identification of ginsenoside metabolites in plasma related to different bioactivities of Panax notoginseng and Panax ginseng

Polish Journal of Veterinary Sciences

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