Pharmacological Evaluation of 3-Carbomethoxy Fentanyl in Mice

• Main Authors: Zeljko Mikovic, Marko Kadija, Cedomir Vucetic, Katarina Savic Vujovic, Ljiljana Dosen-Micovic, Milovan Ivanovic, Sonja Vuckovic, Milica Prostran
• Format: Article
• Language: English
• Published: MDPI AG 2011-01-01
• Series: Pharmaceuticals
• Subjects: fentanyl; 3-carbomethoxy fentanyl; hot plate; rotarod; acute toxicity; mice
• Online Access: http://www.mdpi.com/1424-8247/4/2/233/

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 m 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.