Fig. 5. Administration of 15 mg/kg intraperitoneal (IP) CX717 reverses/prevents fentanyl-induced lethal apnea in adult rats. ( A ) Administration of a high dose of fentanyl (80 μg/kg) over a short period (1 min) induced a profound, lethal respiratory depression. Vehicle (HPCD; 2-hydroxypropyl-β-cyclodextrin) injection before fentanyl administration had no significant effects on depression of respiratory frequency. ( B ) Administration of CX717 (15 mg/kg) within 1 min after the fentanyl infusion reduced the period of apnea and induced the recovery of respiratory rhythm. ( C ) Preadministration of 15 mg/kg IP CX717 before the fentanyl infusion reduced the severity of fentanyl-induced apnea and depression of respiratory frequency and prevented death. ( D ) Population data showing the time course of changes of respiratory frequency in response to fentanyl administration with pre- or postadministration of vehicle or CX717. * P < 0.05 relative to vehicle control respiratory frequency (n = 5 for each group).