Abstract: 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.
Keywords: fentanyl; 3-carbomethoxy fentanyl; hot plate; rotarod; acute toxicity; mice
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Vuckovic, S.; Prostran, M.; Ivanovic, M.; Dosen-Micovic, L.; Vujovic, K.S.; Vucetic, C.; Kadija, M.; Mikovic, Z. Pharmacological Evaluation of 3-Carbomethoxy Fentanyl in Mice. Pharmaceuticals 2011, 4, 233-243.
Vuckovic S, Prostran M, Ivanovic M, Dosen-Micovic L, Vujovic KS, Vucetic C, Kadija M, Mikovic Z. Pharmacological Evaluation of 3-Carbomethoxy Fentanyl in Mice. Pharmaceuticals. 2011; 4(2):233-243.
Vuckovic, Sonja; Prostran, Milica; Ivanovic, Milovan; Dosen-Micovic, Ljiljana; Vujovic, Katarina Savic; Vucetic, Cedomir; Kadija, Marko; Mikovic, Zeljko. 2011. "Pharmacological Evaluation of 3-Carbomethoxy Fentanyl in Mice." Pharmaceuticals 4, no. 2: 233-243.