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The sedative effect of intranasal administration of medetomidine using a mucosal atomization device in Japanese White
Yixian Wei1, I-Ying Chen1, Haruka Tamogi1
1Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Hokkaido, Japan.
Abstract:
To prevent aspiration in Japanese White (JW) rabbits, the maximum single volume of medetomidine administered intranasally is 0.3 mL per nostril using a mucosal atomization device (MAD). This study aimed to examine the sedative effect of intranasal administration of medetomidine using MAD in eight healthy female JW rabbits. Each rabbit received intranasal atomization (INA) of saline (Control treatment) along with three doses of 1 mg/mL medetomidine (0.3 mL to one nostril [MED0.3 treatment]; 0.3 mL each to both nostrils [MED0.6 treatment]; 0.3 mL twice to both nostrils [MED1.2 treatment]), with a washout period of at least 7 days between treatments. The actual doses of medetomidine were 82 (75-84) μg/kg (median [25th-75th percentile]), 163 (156-168) μg/kg, and 323 (295-343) μg/kg for the MED0.3, MED0.6, and MED1.2 treatments, respectively. A medetomidine-dose dependent sedative effect was detected, and the loss of righting reflex (LRR) was achieved in one rabbit at 18 min, seven rabbits at 11 (9-18) min, and eight rabbits at 7 (4-18) min after the MED0.3, MED0.6, and MED1.2 treatments, respectively. The LRR was maintained for 63 (29-71) min and 83 (68-101) min after the MED0.6 and MED1.2 treatments, respectively. Additionally, the INA of medetomidine produced a significant dose-dependent cardiorespiratory depression including a decrease in pulse rate, respiratory rate, percutaneous oxygen saturation, and arterial partial pressure of oxygen, and an increase in arterial partial pressure of carbon dioxide in the rabbits.
Insights
Intranasal medetomidine effectively sedates Japanese White rabbits in a dose-dependent manner, inducing loss of righting reflex. However, higher doses cause significant cardiorespiratory depression, requiring careful monitoring.
Area of Science:
- Veterinary Medicine
- Pharmacology
- Anesthesiology
Background:
- Intranasal medetomidine is used in Japanese White rabbits, with a maximum dose of 0.3 mL per nostril.
- Assessing the sedative effects and safety of intranasal medetomidine administration is crucial for preclinical research.
Purpose of the Study:
- To evaluate the dose-dependent sedative effects of intranasal medetomidine administered via a mucosal atomization device (MAD) in Japanese White rabbits.
- To determine the onset and duration of the loss of righting reflex (LRR) following different doses of intranasal medetomidine.
- To assess the cardiorespiratory effects of intranasal medetomidine in this animal model.
Main Methods:
- Eight healthy female Japanese White rabbits received intranasal atomization (INA) of saline (control) or three doses of medetomidine (0.3 mL, 0.6 mL, 1.2 mL) using MAD.
- Treatments were administered with a minimum 7-day washout period.
- Sedation (LRR) and cardiorespiratory parameters (pulse rate, respiratory rate, oxygen saturation, blood gases) were monitored.
Main Results:
- A dose-dependent sedative effect was observed, with faster onset and longer duration of LRR at higher medetomidine doses.
- The loss of righting reflex was achieved in all rabbits at the highest dose (MED1.2) within 7 minutes.
- Significant dose-dependent cardiorespiratory depression, including decreased pulse and respiratory rates and altered blood oxygen and carbon dioxide levels, was noted.
Conclusions:
- Intranasal medetomidine effectively sedates Japanese White rabbits in a dose-dependent manner.
- The dose and duration of sedation correlate with medetomidine administration volume.
- Cardiorespiratory depression necessitates careful monitoring during and after intranasal medetomidine administration in rabbits.
