Cayman's Forensic Division chemists synthesize reference standards and collaborate with Virginia Commonwealth and Johns Hopkins University researchers to study how fentanyl analogs impact respiratory depression (a leading cause of overdose deaths).

Fatalities from potent fentanyl analogs continue to be a major health concern. This study evaluated the respiratory depressant effects of seven fentanyl analogs that have either emerged in the illicit drug supply or been identified in toxicological analyses following fatal or non-fatal intoxications. Adult male Swiss Webster mice were administered fentanyl analogs (isobutyryl fentanyl, crotonyl fentanyl, para-methoxyfentanyl, para-methoxy-butyryl fentanyl, furanyl fentanyl 3-furancarboxamide isomer, thiophene fentanyl, and benzodioxole fentanyl) and their effects on minute volume as compared to µ-opioid receptor (MOR) agonist standards (fentanyl, morphine, and buprenorphine) were measured using whole body plethysmography (WBP). The results of this study demonstrated that subcutaneously administered fentanyl-related substances elicit hypoventilation in mice with varying potencies and efficacies and that their effects are mediated, at least in part, by the MOR.

Seven fentanyl analogs were investigated alongside fentanyl, morphine, and buprenorphine in Varshneya, N.B., Hassanien, S.H., Holt, M.C., et al. Respiratory depressant effects of fentanyl analogs are opioid receptor-mediated. Biochem. Pharmacol. 114805 (2021).

"The CDC recently reported that for the 12-month period ending March 2021, drug overdose deaths are estimated to be near 100,000 in the United States. Exposure to fentanyl and its many analogs have significantly contributed to this ongoing crisis. Cayman Chemical, as part of our continued commitment to scientific research, was pleased to be part of a multi-disciplinary collaboration geared toward trying to understand the mechanism behind the powerful respiratory depressant effects of these substances that ultimately leads to overdose fatalities." said Donna M. Iula, Ph.D., Vice President of Forensic Chemistry.

Lead author Neil B. Varshneya, Ph.D., said "The Forensic Chemistry Division of Cayman Chemical Company has been a phenomenal research partner in the quest to understand emerging substances of abuse, specifically in their efforts to synthesize high-quality reference standards for the pharmacological characterization of novel synthetic opioids. Through our academic-industrial collaboration, VCU and Cayman added to our collective knowledge of the contributions of fentanyl analogs to the ongoing opioid crisis around the globe and highlighted the need for further research in this area."