TY  - JOUR
AU  - Sonja, Vuckovic
AU  - Katarina, Savic Vujovic
AU  - Ivanović, Milovan
AU  - Došen-Mićović, Ljiljana
AU  - Todorović, Zoran B.
AU  - Vucetic, C.
AU  - Prostran, M.
PY  - 2012
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1276
AB  - 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 Tare 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 mu 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.
AB  - Cilj studije bio je da se ispita neurotoksičnost analoga fentanila: (±)-cis-3-karbometoksi fentanila (C) i (±)-trans-3-karbometoksi fentanil (T) kod pacova. C je oko 2,4-3,1, a T oko 8,4-12,3 puta manje potentan od fentanila u izazivanju antinocicepcije i morfinu-sličnih neurotoksičnih efekata u koje spadaju: refleks ušne školjke, Straub-ov rep, poremećaj motorne koordinacije, katalepsija, gubitak kornealnog refleksa i gubitak refleksa uspravljanja. Svi ispitivani efekti su dozno-zavisni i bivaju poništeni ako se u pretretmanu primeni nalokson, neselektivni antagonist opioidnih receptora, što ukazuje da se efekti odigravaju posredstvom opioidnih receptora. Dalje, F, C i T ispoljavaju sličnu relativnu jačinu u izazivanju ispitivanih efekata, što ukazuje da su slični receptori uključeni u mehanizam antinocicepcije i neurotoksičnih efekata, i to su najverovatnije μ receptori. Kad se primenjuju ekviantinociceptivne doze, C i T izazivaju značajno kraće i antinociceptivno i neurotoksično dejstvo od F. Nisu dokazane značajne razlike u terapijskim indeksima između F, C i T, što ukazuje da su ovi lekovi jednako bezbedni i podnošljivi kad su u pitanju ispitivani neurotoksični efekti. Ispitivanje neurotoksičnosti prikazano u ovom radu može biti korisno u proučavanju odnosa između strukture i aktivnosti hemijski srodnih opioida.
PB  - Veterinary Faculty, Univ Beogradu, Belgrade
T2  - Acta Veterinaria, Beograd
T1  - Neurotoxicity Evaluation of Fentanyl Analogs in Rats
T1  - Ispitivanje neurotoksičnosti analoga fentanila kod pacova
VL  - 62
IS  - 1
SP  - 3
EP  - 15
DO  - 10.2298/AVB1201003V
ER  - 

@article{
author = "Sonja, Vuckovic and Katarina, Savic Vujovic and Ivanović, Milovan and Došen-Mićović, Ljiljana and Todorović, Zoran B. and Vucetic, C. and Prostran, M.",
year = "2012",
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 Tare 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 mu 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., Cilj studije bio je da se ispita neurotoksičnost analoga fentanila: (±)-cis-3-karbometoksi fentanila (C) i (±)-trans-3-karbometoksi fentanil (T) kod pacova. C je oko 2,4-3,1, a T oko 8,4-12,3 puta manje potentan od fentanila u izazivanju antinocicepcije i morfinu-sličnih neurotoksičnih efekata u koje spadaju: refleks ušne školjke, Straub-ov rep, poremećaj motorne koordinacije, katalepsija, gubitak kornealnog refleksa i gubitak refleksa uspravljanja. Svi ispitivani efekti su dozno-zavisni i bivaju poništeni ako se u pretretmanu primeni nalokson, neselektivni antagonist opioidnih receptora, što ukazuje da se efekti odigravaju posredstvom opioidnih receptora. Dalje, F, C i T ispoljavaju sličnu relativnu jačinu u izazivanju ispitivanih efekata, što ukazuje da su slični receptori uključeni u mehanizam antinocicepcije i neurotoksičnih efekata, i to su najverovatnije μ receptori. Kad se primenjuju ekviantinociceptivne doze, C i T izazivaju značajno kraće i antinociceptivno i neurotoksično dejstvo od F. Nisu dokazane značajne razlike u terapijskim indeksima između F, C i T, što ukazuje da su ovi lekovi jednako bezbedni i podnošljivi kad su u pitanju ispitivani neurotoksični efekti. Ispitivanje neurotoksičnosti prikazano u ovom radu može biti korisno u proučavanju odnosa između strukture i aktivnosti hemijski srodnih opioida.",
publisher = "Veterinary Faculty, Univ Beogradu, Belgrade",
journal = "Acta Veterinaria, Beograd",
title = "Neurotoxicity Evaluation of Fentanyl Analogs in Rats, Ispitivanje neurotoksičnosti analoga fentanila kod pacova",
volume = "62",
number = "1",
pages = "3-15",
doi = "10.2298/AVB1201003V"
}

Sonja, V., Katarina, S. V., Ivanović, M., Došen-Mićović, L., Todorović, Z. B., Vucetic, C.,& Prostran, M.. (2012). Neurotoxicity Evaluation of Fentanyl Analogs in Rats. in Acta Veterinaria, Beograd
Veterinary Faculty, Univ Beogradu, Belgrade., 62(1), 3-15.
https://doi.org/10.2298/AVB1201003V

Sonja V, Katarina SV, Ivanović M, Došen-Mićović L, Todorović ZB, Vucetic C, Prostran M. Neurotoxicity Evaluation of Fentanyl Analogs in Rats. in Acta Veterinaria, Beograd. 2012;62(1):3-15.
doi:10.2298/AVB1201003V .

Sonja, Vuckovic, Katarina, Savic Vujovic, Ivanović, Milovan, Došen-Mićović, Ljiljana, Todorović, Zoran B., Vucetic, C., Prostran, M., "Neurotoxicity Evaluation of Fentanyl Analogs in Rats" in Acta Veterinaria, Beograd, 62, no. 1 (2012):3-15,
https://doi.org/10.2298/AVB1201003V . .