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

## TL;DR

This study shows that vatinoxan reduces high blood sugar and excessive urination caused by medetomidine in sedated rats.

## Contribution

Vatinoxan is shown to effectively counteract the adverse effects of medetomidine-based sedation in rats.

## Key findings

- Vatinoxan significantly lowers blood glucose levels in rats treated with medetomidine and midazolam.
- Urine output and glucose concentration are reduced when vatinoxan is administered alongside sedation protocols.
- Fentanyl does not significantly affect blood glucose or urine output in this context.

## Abstract

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 (N = 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 mg/kg) and midazolam (2.0 mg/kg) (MM; N = 8), MM + fentanyl (0.01 mg/kg) (MMF; N = 8), MM vatinoxan (MMV; N = 7), and MMF + vatinoxan (MMFV; N = 8). Blood glucose concentration (BG) was measured repeatedly between 10 and 60 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 min.

Pooled BG was significantly higher in non-vatinoxan treated rats [19.8 ± 3.6 mmol/L (mean ± SD) with MM + MMF compared with 10.3 ± 1.2 mmol/L with MMV + MMFV] (P < 0.001). Similarly, urine output was greater without vatinoxan [median 22.9 (minimum–maximum) 10.6–32.9) vs. 2.8 (0.0–7.4) ml/kg/h] (P < 0.001). Vatinoxan also reduced UG [33.3 (0.6–33.3) vs. 1.4 (0.9–3.2) mmol/L] (P < 0.01) and body weight loss. Fentanyl did not significantly alter these outcomes. Rats were sufficiently sedated after all treatments.

The findings demonstrate that vatinoxan effectively mitigates hyperglycemia, polyuria and glucosuria induced by medetomidine-based sedation protocols in adult, male Wistar rats.

The online version contains supplementary material available at 10.1186/s12917-026-05304-2.