A comparative study on the dependence potential of thienorphine and buprenorphine

Zheng Yong; Yu-Lei Li; Pei-Lan Zhou; Ze-Hui Gong; Rui-Bin Su

doi:10.18203/2319-2003.ijbcp20232560

Authors

Zheng Yong State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China
Yu-Lei Li State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China
Pei-Lan Zhou State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China
Ze-Hui Gong State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China
Rui-Bin Su State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China

DOI:

https://doi.org/10.18203/2319-2003.ijbcp20232560

Keywords:

Thienorphine, Buprenorphine, Oripavine, Opioid addiction

Abstract

Background: As part of research to discover partial opioid agonists for new treatments of opioid abuse and dependency, thienorphine, a buprenorphine analogue, was synthesised and reported to be a potent, long-acting oripavine in multiple mammalian models. Thienorphine binds non-selectively to μ-, δ-, and κ-opioid receptors, and partially stimulates μ- and/or κ-opioid receptors in vitro. Compared with buprenorphine, thienorphine exhibits better analgesic effects and has higher oral bioavailability. Poor oral absorption and dependence have hindered the use of buprenorphine for detoxification therapy and relapse prevention in the clinic. The addiction potential of thienorphine is unknown, and is worthy of in-depth investigation.

Methods: In the present study, we conducted a comparison of thienorphine and buprenorphine with respect to their physical and psychological dependence liabilities, using a naloxone-induced withdrawal test, a conditioned place preference test, and a self-administration experiment in rats.

Results: In contrast to chronic buprenorphine administration, we failed to observe any severe abstinence syndromes in mice or rats treated with thienorphine after naloxone challenge in a physical dependence model. Compared with the dependence potentials of buprenorphine, rats treated with chronic thienorphine did not show a place conditioning response, self-administration, or psychological dependence.

Conclusions: We demonstrated that thienorphine has a lower potential than buprenorphine for physical and psychological dependence. Our results indicate that thienorphine might be a good candidate to treat opioid addiction.

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