Pharmacological Evaluation of 3-Carbomethoxy Fentanyl in Mice

Pharmaceuticals

Sonja Vuckovic¹  Milica Prostran¹  Milovan Ivanovic²  Ljiljana Dosen-Micovic²  Katarina Savic Vujovic¹  Cedomir Vucetic³  Marko Kadija³ 

[1] Department of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine, University of Belgrade, P.O. Box 38, 11129, Belgrade, Serbia;Faculty of Chemistry, University of Belgrade, Belgrade, Serbia;Institute for Orthopaedic Surgery and Traumatology, Clinical Center of Serbia, School of Medicine, University of Belgrade, Belgrade, Serbia

关键词: fentanyl;    3-carbomethoxy fentanyl;    hot plate;    rotarod;    acute toxicity;    mice;   

DOI  :  10.3390/ph4020233

来源: mdpi

【 摘 要 】

In many animal species, as well as in humans, high doses of fentanyl (F) produce marked neurotoxic effects, such as muscular rigidity and respiratory depression. The antinociception (hot-plate test), impairment of motor coordination (rotarod test) and acute toxicity of intraperitoneal newly synthesized analogs, (±)cis-3-carbomethoxy- fentanyl (C) and (±)trans-3-carbomethoxyfentanyl (T) were evaluated in mice. The compounds tested induced antinociception, impairment of performance on the rotarod, and lethality in a dose-dependent manner. The relative order of antinociceptive potency was similar to motor impairment potency, as well as lethality: F > C > T. Naloxone hydrochloride (1 mg/kg; sc) abolished all the effects observed, suggesting that they are mediated via opioid receptors, most probably of μ type. There were no significant differences between the therapeutic indices of F, C and T. It is concluded, the introduction of 3-carbomethoxy group in the piperidine ring of the fentanyl skeleton reduced the potency, but did not affect tolerability and safety of the compound.

【 授权许可】

CC BY   
© 2011 by the authors; licensee MDPI, Basel, Switzerland.