Novel approaches to alleviating opoid-induced side effects in etorphine-immobilised ungulates

Kurzbezeichnung

Alleviating opoid-induced side effects

Einrichtung Vetmeduni

Forschungsinstitut für Wildtierkunde und Ökologie

Art der Forschung

Grundlagenforschung

Forschungsschwerpunkt

Wildtierökologie und -medizin

Abstract

The potent opioid etorphine is essential for the chemical immobilisation of large herbivores. While etorphine induces a rapid and reliable immobilisation, respiratory compromise leading to hypoxaemia, hypercapnia and acidosis remains a significant concern in immobilised wild animals. Etorphine is believed to cause respiratory compromise via mu-receptor activation in the brainstem, as well as inducing an increased sympathetic response leading to pulmonary hypertension. Serotonin agonists, and specifically 5-HT4 receptor agonists, attenuate centrally-mediated opioid-induced respiratory depression as 5-HT4 receptors are co-expressed with mu-opioid receptors on respiratory neurons in the brainstem, but display opposing actions. The 5-HT4 receptor agonist BIMU-8 has shown promise in initial studies aimed at mitigating opioid-induced respiratory depression without affecting sedation or analgesia. It is also thought, that peripherally-acting alpha-2-adrenoceptor antagonists may reduce some of the negative effects of an etorphine-induced sympathetic response, especially in the pulmonary vasculature. In this study, we will investigate whether BIMU-8, and the peripherally-acting alpha-2-antagonist vatinoxan attenuate etorphine-induced respiratory compromise without affecting sedation or leading to additional undesirable physiological changes.