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- Title
NEUROTOXICITY EVALUATION OF FENTANYL ANALOGS IN RATS.
- Authors
Vučković, Sonja; Savić Vujović, Katarina; Ivanović, M.; Došen-Mićović, Ljiljana; Todorović, Z.; Vučetić, C.; Prostran, M.; Prostran, Milica
- Abstract
This study aimed at evaluating the neurotoxicity of fentanyl analogs: (±)-cis-3-carbomethoxy fentanyl (C) and (±)-trans-3- carbomethoxy fentanyl (T) in rats. C and T are less potent (2.4-3.1 and 8.4-12.3 times, respectively) than fentanyl (F) in producing both antinociception and morphine-like neurotoxic effects: loss of pinna reflex, Straub tail, impairment of motor coordination, catalepsy, loss of corneal reflex and loss of righting reflex. All of the effects tested were dose-dependent and they were abolished by pretreatment with naloxone, nonselective antagonist of opioid receptors, indicating that they are mediated via opioid receptors. Further, F, C and T exhibited similar relative potencies in producing all tested effects, indicating that similar receptors are involved in producing antinociceptive and neurotoxic effects, most probably of µ type. By using equiantinociceptive doses, C and T produced significantly shorter duration of both antinociception and neurotoxicity than F. No significant differences between therapeutic indices for F, C and T were found, indicating that these compounds are equally safe and tolerable in respect to the neurotoxic effects tested. Neurotoxicity testing presented in this paper may be useful in studying the structure-activity relationship of opioid congeners.
- Subjects
NEUROTOXICOLOGY; FENTANYL; LABORATORY rats; ANALGESICS; MORPHINE; OPIOID receptors; MOTOR ability; STRUCTURE-activity relationship in pharmacology
- Publication
Acta Veterinaria, 2012, Vol 62, Issue 1, p3
- ISSN
0567-8315
- Publication type
Article
- DOI
10.2298/AVB1201003V