Fig. 5.
The effects of GAL-021 on morphine-induced respiratory acidosis and hypoxia in conscious rats. Respiratory depression was assessed using arterial pH and blood gas analysis. After baseline arterial blood samples had been collected, morphine (10 mg/kg) was administered intravenously to induce respiratory depression. Fifteen to 18 min after morphine administration, GAL-021 (0.03, 0.10, 0.3, and 1.0 mg kg−1 min−1) or vehicle was administered as an intravenous infusion for 20 min. Morphine elicited respiratory depression as evidenced by (A and B) respiratory acidosis (decreased pH and increased Paco2) and (C) hypoxia (decreased Pao2) compared with baseline values. Vehicle infusion and the lowest doses of GAL-021 (0.04 mg kg−1 min−1) had no effect on morphine-induced respiratory depression. The three highest doses of GAL-021 (0.1, 0.3, and 1.0 mg kg−1 min−1) partially restored arterial pH and returned Paco2 to baseline values. Some of the effect of morphine on Pao2 appeared to be transient: Pao2 increased by the end of the vehicle infusion but remained below the baseline value. GAL-021 (0.1 and 1.0 mg kg−1 min−1) increased Pao2 further so that Pao2 was no longer different to baseline values. *Different from baseline values; †different from morphine; ‡different from vehicle; §different from GAL-021 0.04 mg kg−1 min−1; ‖different from GAL-021 0.3 mg kg−1 min−1 (two-way ANOVA with Bonferroni multiple comparisons test, P < 0.05). Values are means ± SD, n = 6 to 11 per group.