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Frączek K, Kowalczyk A, Pekala M, et al. The Positive and Negative Outcome of Morphine and Disulfiram Subacute Co-Administration in Rats in the Absence of Ethanol Challenge. Pharmaceutics. 2020;13(1)doi: 10.3390/pharmaceutics13010029.
Frączek, K., Kowalczyk, A., Pekala, M., Kasarello, K., Sygitowicz, G., Sulejczak, D., Zaremba, M., Konop, M., Frankowska, M., Filip, M., Bujalska-Zadrozny, M., & Kleczkowska, P. (2020). The Positive and Negative Outcome of Morphine and Disulfiram Subacute Co-Administration in Rats in the Absence of Ethanol Challenge. Pharmaceutics, 13(1), . https://doi.org/10.3390/pharmaceutics13010029
Frączek, Karolina, et al. "The Positive and Negative Outcome of Morphine and Disulfiram Subacute Co-Administration in Rats in the Absence of Ethanol Challenge." Pharmaceutics vol. 13,1 (2020). doi: https://doi.org/10.3390/pharmaceutics13010029
Frączek K, Kowalczyk A, Pekala M, Kasarello K, Sygitowicz G, Sulejczak D, Zaremba M, Konop M, Frankowska M, Filip M, Bujalska-Zadrozny M, Kleczkowska P. The Positive and Negative Outcome of Morphine and Disulfiram Subacute Co-Administration in Rats in the Absence of Ethanol Challenge. Pharmaceutics. 2020 Dec 26;13(1). doi: 10.3390/pharmaceutics13010029. PMID: 33375279; PMCID: PMC7823937.
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Pharmaceutics. 2020 Dec 26;13(1). doi: 10.3390/pharmaceutics13010029.

The Positive and Negative Outcome of Morphine and Disulfiram Subacute Co-Administration in Rats in the Absence of Ethanol Challenge.

Pharmaceutics

Karolina Frączek, Agnieszka Kowalczyk, Martyna Pekala, Kaja Kasarello, Grażyna Sygitowicz, Dorota Sulejczak, Malgorzata Zaremba, Marek Konop, Malgorzata Frankowska, Malgorzata Filip, Magdalena Bujalska-Zadrozny, Patrycja Kleczkowska

Affiliations

  1. Centre for Preclinical Research (CBP), Department of Pharmacodynamics, Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland.
  2. Centre for Preclinical Research (CBP), Department of Experimental and Clinical Physiology, Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland.
  3. Department of Clinical Chemistry and Laboratory Diagnostics, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland.
  4. Department of Experimental Pharmacology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawinskiego 5, 02-106 Warsaw, Poland.
  5. Centre for Preclinical Research (CBP), Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland.
  6. Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163 Warsaw, Poland.
  7. Centre for Preclinical Research (CBP), Department of Experimental Physiology and Pathophysiology, Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland.
  8. Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Sm?tna 12, 31-343 Krakow, Poland.

PMID: 33375279 PMCID: PMC7823937 DOI: 10.3390/pharmaceutics13010029

Abstract

Recently, a well-known anti-alcohol agent, disulfiram (DSF), has gain much interest, as it was found to be effective in the treatment of cocaine abusers, thus also giving hope for patients addicted to opioids and other illicit drugs. Therefore, this study was aimed to investigate the possible outcome that might occur within the subacute co-administration of both morphine (MRF) and DSF in rats, but in the absence of ethanol challenge. As observed, intraperitoneal DSF dose-dependently enhanced MRF-mediated analgesia with the maximal efficacy at a dose of 100 mg/kg. Furthermore, MRF-induced tolerance and aggressive behavior were significantly reduced by DSF (100 mg/kg, i.p.) in comparison to MRF solely. Nonetheless, significant blood biochemical markers of hepatotoxicity were found (i.e., alteration in the levels of glutathione, blood urea nitrogen, etc.), following a combination of both drugs. Likewise, histological analysis of liver tissue revealed severe changes in the group of DSF + MRF, which includes swelling, cell death, damage to certain vessels, and hemorrhages into the liver parenchyma. Our findings indicate that DSF should be used with extreme caution, especially within the course of subacute concomitant use with MRF, as several possible side effects may take place.

Keywords: analgesia; disulfiram; hepatotoxicity morphine; side effects

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