Ampakine CX1942 attenuates opioid-induced respiratory depression and corrects the hypoxaemic effects of etorphine in immobilized goats (Capra hircus)

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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.

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