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Isobutyryl-carfentanyl has strong acute toxicity and analgesic effects with high addiction potential.

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Title: Isobutyryl-carfentanyl has strong acute toxicity and analgesic effects with high addiction potential.
Authors: Xu, Deli (AUTHOR), Kuai, Lixin (AUTHOR), Chen, Yuanyuan (AUTHOR), Zeng, Xianbin (AUTHOR), Wang, Dan (AUTHOR), Di, Bin (AUTHOR), Xu, Peng (AUTHOR)
Source: Psychopharmacology. Jan2025, Vol. 242 Issue 1, p205-214. 10p.
Subjects: Drug discrimination (Pharmacology), Subcutaneous injections, Intravenous injections, Intraperitoneal injections, Medical sciences, Fentanyl, Analgesics
Abstract: Rationale: Isobutyryl-carfentanyl is the most recently discovered fentanyl analogue with a chemical structure that is similar to that of carfentanyl. Its analogue, carfentanyl, is regarded as one of the most lethal drugs in the world, with a potency of 10,000 times that of morphine. Therefore, isobutyryl-carfentanyl may possess a comparably high potency and its harmful effects cannot be ignored. Objectives: This study was designed to assess the analgesic effect of isobutyryl-carfentanyl and the potential risks associated with its misuse. Methods: In this study, we assessed the acute toxicity of isobutyryl-carfentanyl by up-and-down-procedure, the analgesic efficacy by hot-plate test, the abuse potential by conditioned place preference (CPP), drug self-administration, and drug discrimination tests, and compared it with fentanyl and carfentanyl. Results: The estimated median lethal dose (LD50) of isobutyryl-carfentanyl administered were 175 mg/kg (intragastric administration, IG), 15.84 mg/kg (intraperitoneal injection, IP), 15.84 mg/kg (subcutaneous injection, SC), and 1.6 mg/kg (intravenous injection, IV), respectively. The 50% maximal analgesic effect (ED50) of isobutyryl-carfentanyl was determined to be 0.00319 mg/kg, with an analgesic potency 14 times that of fentanyl and 0.82 times that of carfentanyl. Isobutyryl-carfentanyl exhibited a significant positional preference at a minimum dose of 0.1 mg/kg, while fentanyl exhibited a significant positional preference at a minimum dose of 0.3 mg/kg. In the heroin (0.05 mg/kg/infusion) self-administration substitution experiment, isobutyryl-carfentanyl showed significant self-administration behaviour at doses of 0.0005–0.001 mg/kg/infusion, with the maximum number of infusions observed at a dose of 0.001 mg/kg. In the heroin (1 mg/kg) drug discrimination experiment, fentanyl (0.005–0.02 mg/kg), carfentanyl (0.0005–0.002 mg/kg), and isobutyryl-carfentanyl (0.001–0.005 mg/kg) were tested in the dose-effect curves. The results showed that all three drugs exhibit dose-dependent increase in the number of drug-associated nose pokes responses and reduction in the rate of nose pokes. The subjective effect potency of isobutyryl-carfentanyl was found to be 4.4 times that of fentanyl and 0.5 times that of carfentanyl. Conclusions: In summary, isobutyryl-carfentanyl has high acute toxicity and analgesic effect, with strong psychological dependence approximately 5 times that of fentanyl and 0.5 times that of carfentanyl, and has extremely high abuse potency. [ABSTRACT FROM AUTHOR]
Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Isobutyryl-carfentanyl has strong acute toxicity and analgesic effects with high addiction potential.
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  Data: <searchLink fieldCode="AR" term="%22Xu%2C+Deli%22">Xu, Deli</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kuai%2C+Lixin%22">Kuai, Lixin</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chen%2C+Yuanyuan%22">Chen, Yuanyuan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zeng%2C+Xianbin%22">Zeng, Xianbin</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wang%2C+Dan%22">Wang, Dan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Di%2C+Bin%22">Di, Bin</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Xu%2C+Peng%22">Xu, Peng</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Psychopharmacology%22">Psychopharmacology</searchLink>. Jan2025, Vol. 242 Issue 1, p205-214. 10p.
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  Data: Rationale: Isobutyryl-carfentanyl is the most recently discovered fentanyl analogue with a chemical structure that is similar to that of carfentanyl. Its analogue, carfentanyl, is regarded as one of the most lethal drugs in the world, with a potency of 10,000 times that of morphine. Therefore, isobutyryl-carfentanyl may possess a comparably high potency and its harmful effects cannot be ignored. Objectives: This study was designed to assess the analgesic effect of isobutyryl-carfentanyl and the potential risks associated with its misuse. Methods: In this study, we assessed the acute toxicity of isobutyryl-carfentanyl by up-and-down-procedure, the analgesic efficacy by hot-plate test, the abuse potential by conditioned place preference (CPP), drug self-administration, and drug discrimination tests, and compared it with fentanyl and carfentanyl. Results: The estimated median lethal dose (LD50) of isobutyryl-carfentanyl administered were 175 mg/kg (intragastric administration, IG), 15.84 mg/kg (intraperitoneal injection, IP), 15.84 mg/kg (subcutaneous injection, SC), and 1.6 mg/kg (intravenous injection, IV), respectively. The 50% maximal analgesic effect (ED50) of isobutyryl-carfentanyl was determined to be 0.00319 mg/kg, with an analgesic potency 14 times that of fentanyl and 0.82 times that of carfentanyl. Isobutyryl-carfentanyl exhibited a significant positional preference at a minimum dose of 0.1 mg/kg, while fentanyl exhibited a significant positional preference at a minimum dose of 0.3 mg/kg. In the heroin (0.05 mg/kg/infusion) self-administration substitution experiment, isobutyryl-carfentanyl showed significant self-administration behaviour at doses of 0.0005–0.001 mg/kg/infusion, with the maximum number of infusions observed at a dose of 0.001 mg/kg. In the heroin (1 mg/kg) drug discrimination experiment, fentanyl (0.005–0.02 mg/kg), carfentanyl (0.0005–0.002 mg/kg), and isobutyryl-carfentanyl (0.001–0.005 mg/kg) were tested in the dose-effect curves. The results showed that all three drugs exhibit dose-dependent increase in the number of drug-associated nose pokes responses and reduction in the rate of nose pokes. The subjective effect potency of isobutyryl-carfentanyl was found to be 4.4 times that of fentanyl and 0.5 times that of carfentanyl. Conclusions: In summary, isobutyryl-carfentanyl has high acute toxicity and analgesic effect, with strong psychological dependence approximately 5 times that of fentanyl and 0.5 times that of carfentanyl, and has extremely high abuse potency. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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