Effects of inhaled aerosolized carfentanil on real-time physiological responses in mice: a preliminary evaluation of naloxone.
This study examined the real-time exposure-response effects of aerosolized carfentanil (CRF) on opioid-induced toxicity, respiratory dynamics and cardiac function in mice. Unrestrained, conscious male CD-1 mice (25-30 g) were exposed to 0.4 or 4.0 mg/m3of aerosolized CRF for 15 min (Ct = 6 or 60 mg min/m3) in a whole-body plethysmograph chamber. Minute volume (MV), core body temperature (Tc), mean arterial blood pressure (MAP) and heart rate (HR) were evaluated in animals exposed to CRF or sterile H2O. Loss of consciousness and Straub tail were observed in before 1 min following initiation of exposure to 6 or 60 mg min/m3of CRF. Clinical signs of opioid-induced toxicity were observed in a dose-dependent manner. Exposure to 6 or 60 mg min/m3of CRF resulted in significant decrease in MV as compared to the controls. MAP, HR and Tcdecreased 24 h in animals exposed to either 6 or 60 mg min/m3of CRF as compared to the controls. Post-exposure administration of naloxone (NX, 0.05 mg/kg, i.m.) did not increase the MV of animals exposed to CRF to control levels within 24 h, but decreased clinical signs of opioid-induced toxicity and the duration of respiratory depression. This is the first study to evaluate real-time respiratory dynamics and cardiac function during exposure and up to 24 h post-exposure to CRF. The evaluation of toxicological signs and respiratory dynamics following exposure to CRF will be useful in the development of therapeutic strategies to counteract the ongoing threat of abuse and overuse of opioids and their synthetic variants.
a Biochemistry and Toxicology Branch , US Army Medical Research Institute of Chemical Defense , Aberdeen Proving Ground , MD , USA.
Benjamin
B
Wong
a Biochemistry and Toxicology Branch , US Army Medical Research Institute of Chemical Defense , Aberdeen Proving Ground , MD , USA.
Michael W
MW
Perkins
a Biochemistry and Toxicology Branch , US Army Medical Research Institute of Chemical Defense , Aberdeen Proving Ground , MD , USA.
Justin
J
Tressler
a Biochemistry and Toxicology Branch , US Army Medical Research Institute of Chemical Defense , Aberdeen Proving Ground , MD , USA.
Ashley
A
Rodriguez
a Biochemistry and Toxicology Branch , US Army Medical Research Institute of Chemical Defense , Aberdeen Proving Ground , MD , USA.
Jennifer
J
Devorak
a Biochemistry and Toxicology Branch , US Army Medical Research Institute of Chemical Defense , Aberdeen Proving Ground , MD , USA.
Alfred M
AM
Sciuto
D000280:Administration, Inhalation; D000336:Aerosols; D000701:Analgesics, Opioid / Q000633:toxicity*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000633:toxicity; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051379:Mice; D009270:Naloxone / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D012131:Respiratory Insufficiency / Q000139:chemically induced / Q000188:drug therapy; D014474:Unconsciousness / Q000139:chemically induced / Q000188:drug therapy
D000336:Aerosols; D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009270:Naloxone; C017114:carfentanil; D005283:Fentanyl
Cardiac function; carfentanil; inhalation exposure; naloxone; respiratory dynamics; respiratory toxicology