Preclinical Assessment of Naloxone Adequacy to Reverse Polysubstance Use-Induced Respiratory Depression In Vivo Validation

Title: Preclinical Assessment of Naloxone Adequacy to Reverse Polysubstance Use-Induced Respiratory Depression In Vivo Validation Agency: U.S. Food and Drug Administration (FDA) Notice Type: Presolicitation: Firm-Fixed Price DEA surveillance data show that street fentanyl is frequently adulterated with xylazine, d-methamphetamine, or alprazolam each of which induces respiratory depression through a distinct mechanism. Approximately 80% of opioid overdose cases involve multiple drugs, yet naloxone the primary FDA-approved reversal agent was developed and tested for opioid-only scenarios. This mechanistic complexity creates uncertainty about naloxone's efficacy in polysubstance overdose and raises the question of what alternative or adjunct therapies may be needed. Drug-induced respiratory c