Neurotoxicity evaluation of fentanyl analogs in rats
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 ne...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Sciendo
2012-01-01
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| Series: | Acta Veterinaria |
| Subjects: | |
| Online Access: | http://www.doiserbia.nb.rs/img/doi/0567-8315/2012/0567-83151201003V.pdf |
| _version_ | 1818525836429492224 |
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| author | Vučković Sonja Vujović-Savić Katarina Ivanović M. Došen-Mićović Ljiljana Todorović Z. Vučetić Č. Prostran M. Prostran Milica |
| author_facet | Vučković Sonja Vujović-Savić Katarina Ivanović M. Došen-Mićović Ljiljana Todorović Z. Vučetić Č. Prostran M. Prostran Milica |
| author_sort | Vučković Sonja |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T06:14:39Z |
| format | Article |
| id | doaj.art-6bced33f64c14f9b90a5e337ad2d583f |
| institution | Directory Open Access Journal |
| issn | 0567-8315 1820-7448 |
| language | English |
| last_indexed | 2024-12-11T06:14:39Z |
| publishDate | 2012-01-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Veterinaria |
| spelling | doaj.art-6bced33f64c14f9b90a5e337ad2d583f2022-12-22T01:18:00ZengSciendoActa Veterinaria0567-83151820-74482012-01-0162131510.2298/AVB1201003VNeurotoxicity evaluation of fentanyl analogs in ratsVučković SonjaVujović-Savić KatarinaIvanović M.Došen-Mićović LjiljanaTodorović Z.Vučetić Č.Prostran M.Prostran MilicaThis 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.http://www.doiserbia.nb.rs/img/doi/0567-8315/2012/0567-83151201003V.pdfanalogfentanylneurotoxicityrats |
| spellingShingle | Vučković Sonja Vujović-Savić Katarina Ivanović M. Došen-Mićović Ljiljana Todorović Z. Vučetić Č. Prostran M. Prostran Milica Neurotoxicity evaluation of fentanyl analogs in rats Acta Veterinaria analog fentanyl neurotoxicity rats |
| title | Neurotoxicity evaluation of fentanyl analogs in rats |
| title_full | Neurotoxicity evaluation of fentanyl analogs in rats |
| title_fullStr | Neurotoxicity evaluation of fentanyl analogs in rats |
| title_full_unstemmed | Neurotoxicity evaluation of fentanyl analogs in rats |
| title_short | Neurotoxicity evaluation of fentanyl analogs in rats |
| title_sort | neurotoxicity evaluation of fentanyl analogs in rats |
| topic | analog fentanyl neurotoxicity rats |
| url | http://www.doiserbia.nb.rs/img/doi/0567-8315/2012/0567-83151201003V.pdf |
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