Effects of vatinoxan and fentanyl on blood glucose concentrations and diuresis in male Wistar rats sedated with medetomidine and midazolam.

Abstract

BACKGROUND: Alpha2-adrenoceptor agonists such as medetomidine induce hyperglycemia, glucosuria, and polyuria. We evaluated the ability of vatinoxan, a peripherally acting alpha2-adrenoceptor antagonist, to mitigate these side effects in male Wistar rats (&#x2009;=&#x2009;31). To explore its impact on two common sedation protocols in laboratory rats, a randomized, controlled experimental study was conducted comprising four groups: medetomidine (0.25&#xa0;mg/kg) and midazolam (2.0&#xa0;mg/kg) (MM;&#x2009;=&#x2009;8), MM&#x2009;+&#x2009;fentanyl (0.01&#xa0;mg/kg) (MMF;&#x2009;=&#x2009;8), MM vatinoxan (MMV;&#x2009;=&#x2009;7), and MMF&#x2009;+&#x2009;vatinoxan (MMFV;&#x2009;=&#x2009;8). Blood glucose concentration (BG) was measured repeatedly between 10 and 60&#xa0;min after treatment administration, and total urine output and body weight change were assessed. Additionally, urine glucose concentration (UG) was measured at 45 and 75&#xa0;min. RESULTS: Pooled BG was significantly higher in non-vatinoxan treated rats [19.8&#x2009;&#xb1;&#x2009;3.6 mmol/L (mean&#x2009;&#xb1;&#x2009;SD) with MM&#x2009;+&#x2009;MMF compared with 10.3&#x2009;&#xb1;&#x2009;1.2 mmol/L with MMV&#x2009;+&#x2009;MMFV] (&#x2009;<&#x2009;0.001). Similarly, urine output was greater without vatinoxan [median 22.9 (minimum&#x2013;maximum) 10.6&#x2013;32.9) vs. 2.8 (0.0&#x2013;7.4) ml/kg/h] (&#x2009;<&#x2009;0.001). Vatinoxan also reduced UG [33.3 (0.6&#x2013;33.3) vs. 1.4 (0.9&#x2013;3.2) mmol/L] (&#x2009;<&#x2009;0.01) and body weight loss. Fentanyl did not significantly alter these outcomes. Rats were sufficiently sedated after all treatments. CONCLUSIONS: The findings demonstrate that vatinoxan effectively mitigates hyperglycemia, polyuria and glucosuria induced by medetomidine-based sedation protocols in adult, male Wistar rats. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12917-026-05304-2.