E161111 is an ultra-short-acting etomidate analogue with stable haemodynamics that elicits only slight adrenocortical suppression in rats
Purpose We report on a novel ultra-short-acting etomidate analogue, E161111, which has the same primary metabolite as etomidate. Methods The metabolic rate of E161111 was determined in rat plasma and liver homogenate. Rats were infused for 30 or 60 min to maintain light sedation at Richmond Agitatio...
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PeerJ Inc.
2022-05-01
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| Online Access: | https://peerj.com/articles/13492.pdf |
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| author | Bin Wang Deying Gong Yi Kang Jin Liu Jun Yang Wen-sheng Zhang |
| author_facet | Bin Wang Deying Gong Yi Kang Jin Liu Jun Yang Wen-sheng Zhang |
| author_sort | Bin Wang |
| collection | DOAJ |
| description | Purpose We report on a novel ultra-short-acting etomidate analogue, E161111, which has the same primary metabolite as etomidate. Methods The metabolic rate of E161111 was determined in rat plasma and liver homogenate. Rats were infused for 30 or 60 min to maintain light sedation at Richmond Agitation-Sedation Scale (RASS) for −2 to 0 score. Mean arterial pressure (MAP) was monitored during 30 min infusion. The serum corticosterone was determined during and 3 h after infusion as a measure of adrenocortical function. Results E161111 was not detected in rat plasma at 1 min (t1/2 = 6.69 ± 0.07 s) and in rat liver homogenates at 5 min (t1/2 = 10.20 ± 3.76 s); its main metabolic product was etomidate acid. The recovery time from loss of righting reflex (LORR) was 4.3 ± 1.5 min after 1-h infusion of E161111. During 30 min infusion, E161111 did not cause MAP changes. The stimulated serum corticosterone levels after 1-h infusion of E161111 were significantly higher than that after 1-h infusion of etomidate at all time points tested for the 3 h study. Conclusions E161111 was metabolised rapidly, the metabolites were same as etomidate, and the recovery time after 1-h infusion was short. It elicited haemodynamic stability and milder suppression of corticosterone than that elicited by etomidate. |
| first_indexed | 2024-03-09T08:18:31Z |
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| id | doaj.art-5c94fbd71f1140acb6b38cffd3c7fdd4 |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T08:18:31Z |
| publishDate | 2022-05-01 |
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| spelling | doaj.art-5c94fbd71f1140acb6b38cffd3c7fdd42023-12-02T21:58:46ZengPeerJ Inc.PeerJ2167-83592022-05-0110e1349210.7717/peerj.13492E161111 is an ultra-short-acting etomidate analogue with stable haemodynamics that elicits only slight adrenocortical suppression in ratsBin Wang0Deying Gong1Yi Kang2Jin Liu3Jun Yang4Wen-sheng Zhang5Department of Anesthesiology, People’s Hospital of Guizhou Province, Guiyang, Guizhou, ChinaLaboratory of Anaesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaLaboratory of Anaesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaLaboratory of Anaesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaLaboratory of Anaesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaLaboratory of Anaesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaPurpose We report on a novel ultra-short-acting etomidate analogue, E161111, which has the same primary metabolite as etomidate. Methods The metabolic rate of E161111 was determined in rat plasma and liver homogenate. Rats were infused for 30 or 60 min to maintain light sedation at Richmond Agitation-Sedation Scale (RASS) for −2 to 0 score. Mean arterial pressure (MAP) was monitored during 30 min infusion. The serum corticosterone was determined during and 3 h after infusion as a measure of adrenocortical function. Results E161111 was not detected in rat plasma at 1 min (t1/2 = 6.69 ± 0.07 s) and in rat liver homogenates at 5 min (t1/2 = 10.20 ± 3.76 s); its main metabolic product was etomidate acid. The recovery time from loss of righting reflex (LORR) was 4.3 ± 1.5 min after 1-h infusion of E161111. During 30 min infusion, E161111 did not cause MAP changes. The stimulated serum corticosterone levels after 1-h infusion of E161111 were significantly higher than that after 1-h infusion of etomidate at all time points tested for the 3 h study. Conclusions E161111 was metabolised rapidly, the metabolites were same as etomidate, and the recovery time after 1-h infusion was short. It elicited haemodynamic stability and milder suppression of corticosterone than that elicited by etomidate.https://peerj.com/articles/13492.pdfEtomidate analogueSoft drugAdrenocortical suppressionUltra-short-actingContinuous infusionStable haemodynamics |
| spellingShingle | Bin Wang Deying Gong Yi Kang Jin Liu Jun Yang Wen-sheng Zhang E161111 is an ultra-short-acting etomidate analogue with stable haemodynamics that elicits only slight adrenocortical suppression in rats PeerJ Etomidate analogue Soft drug Adrenocortical suppression Ultra-short-acting Continuous infusion Stable haemodynamics |
| title | E161111 is an ultra-short-acting etomidate analogue with stable haemodynamics that elicits only slight adrenocortical suppression in rats |
| title_full | E161111 is an ultra-short-acting etomidate analogue with stable haemodynamics that elicits only slight adrenocortical suppression in rats |
| title_fullStr | E161111 is an ultra-short-acting etomidate analogue with stable haemodynamics that elicits only slight adrenocortical suppression in rats |
| title_full_unstemmed | E161111 is an ultra-short-acting etomidate analogue with stable haemodynamics that elicits only slight adrenocortical suppression in rats |
| title_short | E161111 is an ultra-short-acting etomidate analogue with stable haemodynamics that elicits only slight adrenocortical suppression in rats |
| title_sort | e161111 is an ultra short acting etomidate analogue with stable haemodynamics that elicits only slight adrenocortical suppression in rats |
| topic | Etomidate analogue Soft drug Adrenocortical suppression Ultra-short-acting Continuous infusion Stable haemodynamics |
| url | https://peerj.com/articles/13492.pdf |
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