ArticlePloS one2022
Characterization of intracellular calcium mobilization induced by remimazolam, a newly approved intravenous anesthetic.
Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 17 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- RemimazolamPeerJ · 2026Pooled it
- Beneficial Effects of Remimazolam Compared with Dexmedetomidine as an Adjuvant in Total Intravenous Anaesthesia with Propofol and Remifentanil: A Randomised Controlled Trial.Medicina (Kaunas, Lithuania) · 2026Trial
- Patient-Controlled Sedation with Remimazolam Enables More Precise Intraoperative Sedation in Elderly Patients Under Spinal Anesthesia: A Randomized Controlled Trial.Drug design, development and therapy · 2026Trial
- Effect of remimazolam on intraoperative hemodynamic stability in patients undergoing cerebrovascular bypass surgery: a prospective randomized controlled trial.Korean journal of anesthesiology · 2025Trial
- Comparison of the recovery time of remimazolam besylate and propofol for gastrointestinal endoscopy sedation in elderly patients.International journal of medical sciences · 2024Trial
- Comparison of Remimazolam versus Sevoflurane on the Postoperative Quality of Recovery in Cervical Spine Surgery: A Prospective Randomized Controlled Double-Blind Trial.Drug design, development and therapy · 2024Trial
- Effects of Remimazolam Anesthesia in Patients Undergoing Deep Inferior Epigastric Perforator Flap Reconstruction for Breast Cancer: A Retrospective Cohort Study.International journal of medical sciences · 2026Article
- Clinically Relevant Doses of Remimazolam Modulate Cardiac Electrophysiology: Late Repolarization Prolongation and Increased Conduction Dispersion With Preserved QTc.Cardiology research and practice · 2026Article
- Review
- Efficacy and safety of continuous infusion of remimazolam for sedation in elderly patients undergoing colonoscopic polypectomy: A non-inferiority prospective controlled clinical trial.Journal of anesthesia and translational medicine · 2025Article
- Clinical Experience With Remimazolam in Neuroanesthesiology and Neurocritical Care: An Educational Focused Review.Journal of clinical medicine research · 2025Review
- Quality of Postoperative Recovery in Total Intravenous Anesthesia between Remimazolam and Propofol for Intraoperative Neurophysiological Monitoring: A Prospective Double-Blind Randomized Controlled Trial.Journal of personalized medicine · 2024Article
- Article
- Effects of different doses of remimazolam on the quality of sedation and cardiac function in elderly patients: a double-blind randomised controlled study.Frontiers in cardiovascular medicine · 2024Article
- Article
- Article
- Remimazolam - current knowledge on a new intravenous benzodiazepine anesthetic agent.Korean journal of anesthesiology · 2022Review
Corrections and comments
- Expression of concern · 2023-01-11Conflict of Interest ·
- Expression of concern
Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many anesthetics, including Propofol, have been reported to induce elevation of intracellular calcium, and we were interested to investigate the possible contribution of calcium elevation to the mechanism of the newly approved remimazolam actions. Remimazolam is an intravenous anesthetic first approved in Japan in July 2020, and is thought to exert its anesthetic actions via γ-aminobutyric acid A (GABAA) receptors; however, the precise mechanisms of how remimazolam elevates intracellular calcium levels remains unclear. We examined the remimazolam-induced elevation of intracellular calcium using SHSY-5Y neuroblastoma cells, COS-7 cells, HEK293 cells, HeLa cells, and human umbilical vein endothelial cells (HUVECs) loaded with fluorescent dyes for live imaging. We confirmed that high concentrations of remimazolam (greater than 300 μM) elevated intracellular calcium in a dose-dependent manner in these cells tested. This phenomenon was not influenced by elimination of extracellular calcium. The calcium elevation was abolished when intracellular or intraendoplasmic reticulum (ER) calcium was depleted by BAPTA-AM or thapsigargin, respectively, suggesting that calcium was mobilized from the ER. Inhibitors of G-protein coupled receptors (GPCRs)-mediated signals, including U-73122, a phospholipase C (PLC) inhibitor and xestospongin C, an inositol 1,4,5-triphosphate receptors (IP3R) antagonist, significantly suppressed remimazolam-induced calcium elevation, whereas dantrolene, a ryanodine receptor antagonist, did not influence remimazolam-induced calcium elevation. Meanwhile, live imaging of ER during remimazolam stimulation using ER-tracker showed no morphological changes. These results suggest that high doses of remimazolam increased intracellular calcium concentration in a dose-dependent manner in each cell tested, which was predicted to be caused by calcium mobilization from the ER. In addition, our studies using various inhibitors revealed that this calcium elevation might be mediated by the GPCRs-IP3 pathway. However, further studies are required to identify which type of GPCRs is involved.
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