Anna J Haw1, Leith Cr Meyer1,2, John J Greer3, Andrea Fuller1,2. 1. Brain Function Research Group, Faculty of Health Sciences, School of Physiology, University of the Witwatersrand, Parktown, South Africa. 2. Department of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, South Africa. 3. Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
Abstract
OBJECTIVES: To determine whether CX1942 reverses respiratory depression in etorphine-immobilized goats, and to compare its effects with those of doxapram hydrochloride. STUDY DESIGN: A prospective, crossover experimental trial conducted at 1753 m.a.s.l. ANIMALS: Eight adult female Boer goats (Capra hircus) with a mean ± standard deviation mass of 27.1 ± 1.6 kg. METHODS: Following immobilization with 0.1 mg kg(-1) etorphine, goats received one of doxapram, CX1942 or sterile water intravenously, in random order in three trials. Respiratory rate, ventilation and tidal volume were measured continuously. Arterial blood samples for the determination of PaO2 , PaCO2 , pH and SaO2 were taken 2 minutes before and then at 5 minute intervals after drug administration for 25 minutes. RESULTS: Doxapram corrected etorphine-induced respiratory depression but also led to arousal and hyperventilation at 2 minutes after its administration, as indicated by the low PaCO2 (27.8 ± 4.5 mmHg) and ventilation of 5.32 ± 5.24 L minute(-1) above pre-immobilization values. CX1942 improved respiratory parameters and corrected etorphine's hypoxaemic effects more gradually than did doxapram, with a more sustained improvement in PaO2 and SaO2 in comparison with the control trial. CONCLUSIONS: CX1942 attenuated opioid-induced respiratory depression and corrected the hypoxaemic effects of etorphine in immobilized goats. CLINICAL RELEVANCE: Ampakines potentially offer advantages over doxapram, a conventional treatment, in reversing etorphine-induced respiratory depression without causing unwanted side effects, particularly arousal, in immobilized animals.
OBJECTIVES: To determine whether CX1942 reverses respiratory depression in etorphine-immobilized goats, and to compare its effects with those of doxapram hydrochloride. STUDY DESIGN: A prospective, crossover experimental trial conducted at 1753 m.a.s.l. ANIMALS: Eight adult female Boer goats (Capra hircus) with a mean ± standard deviation mass of 27.1 ± 1.6 kg. METHODS: Following immobilization with 0.1 mg kg(-1) etorphine, goats received one of doxapram, CX1942 or sterile water intravenously, in random order in three trials. Respiratory rate, ventilation and tidal volume were measured continuously. Arterial blood samples for the determination of PaO2 , PaCO2 , pH and SaO2 were taken 2 minutes before and then at 5 minute intervals after drug administration for 25 minutes. RESULTS:Doxapram corrected etorphine-induced respiratory depression but also led to arousal and hyperventilation at 2 minutes after its administration, as indicated by the low PaCO2 (27.8 ± 4.5 mmHg) and ventilation of 5.32 ± 5.24 L minute(-1) above pre-immobilization values. CX1942 improved respiratory parameters and corrected etorphine's hypoxaemic effects more gradually than did doxapram, with a more sustained improvement in PaO2 and SaO2 in comparison with the control trial. CONCLUSIONS: CX1942 attenuated opioid-induced respiratory depression and corrected the hypoxaemic effects of etorphine in immobilized goats. CLINICAL RELEVANCE: Ampakines potentially offer advantages over doxapram, a conventional treatment, in reversing etorphine-induced respiratory depression without causing unwanted side effects, particularly arousal, in immobilized animals.
Authors: Paulina M Getsy; Santhosh M Baby; Walter J May; James N Bates; Christopher R Ellis; Michael G Feasel; Christopher G Wilson; Tristan H J Lewis; Benjamin Gaston; Yee-Hsee Hsieh; Stephen J Lewis Journal: Front Pharmacol Date: 2022-09-28 Impact factor: 5.988