biostudies-literatureUnknown7(3)Shahbazi Nia STexas Tech UniversityOpioids represent the most extensive category of abused substances in the United States, and the number of fatalities caused by these drugs exceeds those associated with all other drug overdoses combined. The administration of naltrexone, a potent pan-opioid receptor antagonist, to an individual dependent on opioids can trigger opioid withdrawal and induce severe side effects. There is a pressing demand for opioid antagonists free of opioid withdrawal effects. In our laboratory, we have identified a compound with affinity to mu, delta, and kappa opioid receptors in the range of 150-250 nM. This blood-brain barrier (BBB)-permeant compound was metabolically stable <i>in vitro</i> and <i>in vivo</i>. Our <i>in vivo</i> work demonstrated that 1-10 mg/kg intraperitoneal administration of our compound produces moderate efficacy in antagonizing morphine-induced antiallodynia effects in the chemotherapy-induced peripheral neuropathy (CIPN) model. The treatment was well-tolerated and did not cause behavioral changes. We have observed a fast elimination rate of this metabolically stable molecule. Furthermore, no organ toxicity was observed during the chronic administration of the compound over a 14-day period. Overall, we report a novel functional opioid antagonist holds promise for developing an opioid withdrawal therapeutic.ACS pharmacology & translational science654-666https://www.ebi.ac.uk/biostudies/studies/S-EPMC10928894biostudies-literatureCharacterization of a Nonselective Opioid Receptor Functional Antagonist: Implications for Development as a Novel Opioid Dependence Medication.PMC10928894McMahon LRShahi SPatel DWilkerson JLZuarth Gonzalez JDBandy RThompson JOrtiz YTGerman NADiab HHossain MAFrimpong-Manson KShamir LShahbazi Nia SBhat AfalseCharacterization of a Nonselective Opioid Receptor Functional Antagonist: Implications for Development as a Novel Opioid Dependence Medication.Opioids represent the most extensive category of abused substances in the United States, and the number of fatalities caused by these drugs exceeds those associated with all other drug overdoses combined. The administration of naltrexone, a potent pan-opioid receptor antagonist, to an individual dependent on opioids can trigger opioid withdrawal and induce severe side effects. There is a pressing demand for opioid antagonists free of opioid withdrawal effects. In our laboratory, we have identified a compound with affinity to mu, delta, and kappa opioid receptors in the range of 150-250 nM. This blood-brain barrier (BBB)-permeant compound was metabolically stable <i>in vitro</i> and <i>in vivo</i>. Our <i>in vivo</i> work demonstrated that 1-10 mg/kg intraperitoneal administration of our compound produces moderate efficacy in antagonizing morphine-induced antiallodynia effects in the chemotherapy-induced peripheral neuropathy (CIPN) model. The treatment was well-tolerated and did not cause behavioral changes. We have observed a fast elimination rate of this metabolically stable molecule. Furthermore, no organ toxicity was observed during the chronic administration of the compound over a 14-day period. Overall, we report a novel functional opioid antagonist holds promise for developing an opioid withdrawal therapeutic.2024-01-01T00:00:00Z2024 Mar2025-04-18T13:01:04.236Z2025-04-06T22:28:35.763ZS-EPMC109288943848168810.1021/acsptsci.3c00262