Leila G. Shamir

Texas Tech University

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Lance Richard McMahon

Texas Tech University Health Sciences Center

Jenny L. Wilkerson

University of Florida

Yuma T. Ortiz

University of Florida

J. E. Thompson

Texas Tech University

Nadezhda German

Texas Tech University Health Sciences Center

Anoushka Bhat

Texas Tech University Health Sciences Center

Kofi Frimpong-Manson

Texas Tech University Health Sciences Center

Sadisna Shahi

Texas Tech University Health Sciences Center

Siavash Shahbazi Nia

Purdue University West Lafayette

Mohammad Anwar Hossain

University of North Carolina at Chapel Hill

Cooperative Institutions

Texas Tech University

Texas Tech University Health Sciences Center

University of Florida

Samford University

National Institute on Drug Abuse

National Institutes of Health

University of South Carolina

Florida College

The University of Texas at San Antonio

The University of Texas Health Science Center at San Antonio

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Characterization of a Nonselective Opioid Receptor Functional Antagonist: Implications for Development as a Novel Opioid Dependence Medication

ACS Pharmacology & Translational Science (2024)

Siavash Shahbazi Nia Yuma T. Ortiz Julio D. Zuarth Gonzalez Leila G. Shamir Kofi Frimpong-Manson

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 in vitro and in vivo. Our in vivo 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.

Opioid antagonist

10.1021/acsptsci.3c00262

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Characterization of commercially available murine fibrosarcoma NCTC-2472 cells both in vitro and as a model of bone cancer pain in vivo

PLoS ONE (2024)

Yuma T. Ortiz Leila G. Shamir Lance Richard McMahon Jenny L. Wilkerson

For many cancer patients tumor burden negatively impacts quality of life due to associated pain onset. Neuropathic pain is commonly associated with late cancer stages, and is resultant of tumor metastasis to bone, herein referred to as cancer-induced bone pain. Given the severe impact on quality of life and clinical treatment strategies focusing on symptom management, novel therapeutics are needed to alleviate cancer-induced bone pain and/or reduce cancer burden. In the current study we characterized a commercially available murine fibrosarcoma cell line, NCTC-2472 in vitro , which can be used to assess the capacity of novel compounds to impact cellular viability. We found that dimethyl sulfoxide, a known cytotoxic agent and common drug preparation compound, significantly decreased cell viability in a dose-related manner. We then characterized the in vivo tumor development and associated pain behavior characteristics following implantation of NCTC-2472 fibrosarcoma into male and female C3H/HeJ mice. The C3H/HeJ strain was utilized as these mice are syngeneic with NCTC-2472 fibrosarcoma and their use reduces potential implantation failure. We found that tumor development in mice resulted in the development of mechanical allodynia but not thermal hyperalgesia. Gabapentin, a clinically relevant analgesic, produced dose-related mechanical allodynia reversal. These studies provide further characterization of a cancer-induced bone pain model that can be used to examine novel compounds as anti-cancer and analgesic therapeutics.

Bone cancer

10.1371/journal.pone.0309398

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