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Pharmaceuticals 2011, 4(2), 233-243; doi:10.3390/ph4020233
Article

Pharmacological Evaluation of 3-Carbomethoxy Fentanyl in Mice

1,* , 1, 2, 2, 1, 3, 3 and 4
1 Department of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine, University of Belgrade, P.O. Box 38, 11129, Belgrade, Serbia 2 Faculty of Chemistry, University of Belgrade, Belgrade, Serbia 3 Institute for Orthopaedic Surgery and Traumatology, Clinical Center of Serbia, School of Medicine, University of Belgrade, Belgrade, Serbia 4 Department of High-Risk Pregnancies, University Clinic of Gynaecology and Obstetrics “Narodni Front”, Belgrade, Serbia
* Author to whom correspondence should be addressed.
Received: 15 December 2010 / Revised: 13 January 2011 / Accepted: 18 January 2011 / Published: 25 January 2011
(This article belongs to the Special Issue Opioids)
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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 fentanyl; 3-carbomethoxy fentanyl; hot plate; rotarod; acute toxicity; mice
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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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.

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