Related Experiment Video
Updated: Feb 9, 2026

Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain
Published on: January 4, 2018
Peripheral α2-adrenoceptor antagonism affects the absorption of intramuscularly coadministered drugs
Ira J Kallio-Kujala1, Marja R Raekallio1, Juhana Honkavaara1
1Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.
Objective:
We determined the possible effects of a peripherally acting α2-adrenoceptor antagonist, MK-467, on the absorption of intramuscularly (IM) coadministered medetomidine, butorphanol and midazolam.
Study Design:
Randomized, experimental, blinded crossover study.
Animals:
Six healthy Beagle dogs.
Methods:
Two IM treatments were administered: 1) medetomidine hydrochloride (20 μg kg-1) + butorphanol (100 μg kg-1) + midazolam (200 μg kg-1; MBM) and 2) MBM + MK-467 hydrochloride (500 μg kg-1; MBM-MK), mixed in a syringe. Heart rate was recorded at regular intervals. Sedation was assessed with visual analog scales (0-100 mm). Drug concentrations in plasma were analyzed with liquid chromatography-tandem mass spectrometry, with chiral separation of dex- and levomedetomidine. Maximum drug concentrations in plasma (Cmax) and time to Cmax (Tmax) were determined. Paired t-tests, with Bonferroni correction when appropriate, were used for comparisons between the treatments.
Results:
Data from five dogs were analyzed. Heart rate was significantly higher from 20 to 90 minutes after MBM-MK. The Tmax values for midazolam and levomedetomidine (mean ± standard deviation) were approximately halved with coadministration of MK-467, from 23 ± 9 to 11 ± 6 minutes (p = 0.049) for midazolam and from 32 ± 15 to 18 ± 6 minutes for levomedetomidine (p = 0.036), respectively.
Conclusions And Clinical Relevance:
MK-467 accelerated the absorption of IM coadministered drugs. This is clinically relevant as it may hasten the onset of peak sedative effects.
More Related Videos
Related Concept Videos
Combined Effects of Drugs: Antagonism
The most common type is receptor antagonism, where one drug acts as an antagonist to block the effects of another drug by...
Drug Absorption: Factors Affecting GI Absorption
Antiasthma Drugs: β2-Adrenoceptor Agonists
One class of bronchodilators includes β2-adrenoceptor agonists. These agents target the β2-adrenoceptors located on bronchial smooth muscle cells. By stimulating these receptors, β2-agonists induce...
Drug Absorption: Overview
When drugs are injected intravenously, they directly enter the systemic circulation. Alternatively, orally administered drugs navigate through the gastrointestinal (GI)...
Factors Influencing Drug Absorption: Drug Dissolution
Methods for Studying Drug Absorption: In situ
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...

