TY  - JOUR
AU  - Vujovic, Katarina R. Savic
AU  - Vuckovic, Sonja
AU  - Srebro, Dragana
AU  - Ivanović, Milovan
AU  - Došen-Mićović, Ljiljana
AU  - Vucetic, Cedomir
AU  - Dzoljic, Eleonora
AU  - Prostran, Milica
PY  - 2013
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1633
AB  - In addition to producing antinociception, opioids exert profound effects on body temperature. This study aimed at comparing antinociceptive and hyperthermic responses between two groups of mu-opioid receptor agonists: fentanyl (4-anilinopiperidine-type) and morphine (phenanthrene-type) derivatives in rats. Analgesic activity was assessed by tail immersion test and the body temperature by insertion of a thermometer probe into the colon. Fentanyl (F), (+/-)-cis-3-methyl fentanyl (CM), (+/-)-cis-3-carbomethoxy fentanyl (C), (+/-)trans-3-carbomethoxy fentanyl (T) and (+/-)-cis-3 butyl fentanyl (B) produced dose-dependent increase in antinociception and hyperthermia. The relative order of analgesic potency was: CM(11.27) gt  F(1) gt  C(0.35)a parts per thousand yenT(0.11)a parts per thousand yenB(0.056). Similar to this, the relative order of hyperthermic potency was: CM(8.43) gt  F(1) gt  C(0.46)a parts per thousand yenT(0.11)a parts per thousand yenB(0.076). Morphine (M), oxycodone (O), thebacon (T) and 6,14-ethenomorphinan-7-methanol, 4,5-epoxy-6-fluoro-3-hydroxy-alpha,alpha,17-trimethyl-, (5 alpha,7 alpha) (E) also produced dose-dependent increase in antinociception and hyperthermia. Among morphine derivatives the relative order of analgesic potency was: E(56) gt  O(5)a parts per thousand yenT(2.6) gt  M(1), and similar to this, the relative order of hyperthermic potency was: E(37) gt  O(3)a parts per thousand yenT(2.3) gt  M(1). Morphine (phenanthrene-type) and fentanyl (4-anilinopiperidine-type) derivatives produced hyperthermia in rats at doses about 2 times lower, and 6-11 times higher, than their median antinociceptive doses, respectively. This study is first to identify difference between these two classes of opioid drugs in their potencies in producing hyperthermia. Further studies are needed to clarify the significance of these findings.
PB  - Pharmaceutical Soc Korea, Seoul
T2  - Archives of Pharmacal Research
T1  - A comparison of the antinociceptive and temperature responses to morphine and fentanyl derivatives in rats
VL  - 36
IS  - 4
SP  - 501
EP  - 508
DO  - 10.1007/s12272-013-0072-z
ER  - 

@article{
author = "Vujovic, Katarina R. Savic and Vuckovic, Sonja and Srebro, Dragana and Ivanović, Milovan and Došen-Mićović, Ljiljana and Vucetic, Cedomir and Dzoljic, Eleonora and Prostran, Milica",
year = "2013",
abstract = "In addition to producing antinociception, opioids exert profound effects on body temperature. This study aimed at comparing antinociceptive and hyperthermic responses between two groups of mu-opioid receptor agonists: fentanyl (4-anilinopiperidine-type) and morphine (phenanthrene-type) derivatives in rats. Analgesic activity was assessed by tail immersion test and the body temperature by insertion of a thermometer probe into the colon. Fentanyl (F), (+/-)-cis-3-methyl fentanyl (CM), (+/-)-cis-3-carbomethoxy fentanyl (C), (+/-)trans-3-carbomethoxy fentanyl (T) and (+/-)-cis-3 butyl fentanyl (B) produced dose-dependent increase in antinociception and hyperthermia. The relative order of analgesic potency was: CM(11.27) gt  F(1) gt  C(0.35)a parts per thousand yenT(0.11)a parts per thousand yenB(0.056). Similar to this, the relative order of hyperthermic potency was: CM(8.43) gt  F(1) gt  C(0.46)a parts per thousand yenT(0.11)a parts per thousand yenB(0.076). Morphine (M), oxycodone (O), thebacon (T) and 6,14-ethenomorphinan-7-methanol, 4,5-epoxy-6-fluoro-3-hydroxy-alpha,alpha,17-trimethyl-, (5 alpha,7 alpha) (E) also produced dose-dependent increase in antinociception and hyperthermia. Among morphine derivatives the relative order of analgesic potency was: E(56) gt  O(5)a parts per thousand yenT(2.6) gt  M(1), and similar to this, the relative order of hyperthermic potency was: E(37) gt  O(3)a parts per thousand yenT(2.3) gt  M(1). Morphine (phenanthrene-type) and fentanyl (4-anilinopiperidine-type) derivatives produced hyperthermia in rats at doses about 2 times lower, and 6-11 times higher, than their median antinociceptive doses, respectively. This study is first to identify difference between these two classes of opioid drugs in their potencies in producing hyperthermia. Further studies are needed to clarify the significance of these findings.",
publisher = "Pharmaceutical Soc Korea, Seoul",
journal = "Archives of Pharmacal Research",
title = "A comparison of the antinociceptive and temperature responses to morphine and fentanyl derivatives in rats",
volume = "36",
number = "4",
pages = "501-508",
doi = "10.1007/s12272-013-0072-z"
}

Vujovic, K. R. S., Vuckovic, S., Srebro, D., Ivanović, M., Došen-Mićović, L., Vucetic, C., Dzoljic, E.,& Prostran, M.. (2013). A comparison of the antinociceptive and temperature responses to morphine and fentanyl derivatives in rats. in Archives of Pharmacal Research
Pharmaceutical Soc Korea, Seoul., 36(4), 501-508.
https://doi.org/10.1007/s12272-013-0072-z

Vujovic KRS, Vuckovic S, Srebro D, Ivanović M, Došen-Mićović L, Vucetic C, Dzoljic E, Prostran M. A comparison of the antinociceptive and temperature responses to morphine and fentanyl derivatives in rats. in Archives of Pharmacal Research. 2013;36(4):501-508.
doi:10.1007/s12272-013-0072-z .

Vujovic, Katarina R. Savic, Vuckovic, Sonja, Srebro, Dragana, Ivanović, Milovan, Došen-Mićović, Ljiljana, Vucetic, Cedomir, Dzoljic, Eleonora, Prostran, Milica, "A comparison of the antinociceptive and temperature responses to morphine and fentanyl derivatives in rats" in Archives of Pharmacal Research, 36, no. 4 (2013):501-508,
https://doi.org/10.1007/s12272-013-0072-z . .

TY  - JOUR
AU  - Vučković, Sonja M.
AU  - Savić-Vujović, Katarina
AU  - Srebro, Dragana
AU  - Ivanović, Milovan
AU  - Došen-Mićović, Ljiljana
AU  - Stojanović, Radan
AU  - Prostran, Milica
PY  - 2012
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/140
AB  - Introduction. Fentanyl belongs to 4-anilidopiperidine class of synthetic opioid analgesics. It is characterized by high potency, rapid onset and short duration of action. A large number of fentanyl analogues have been synthesized so far, both to establish the structure-activity-relationship (SAR) and to find novel, clinically useful analgesic drugs. Objective. In this study, newly synthesized 3-alkyl fentanyl analogues were examined for analgesic activity and compared with fentanyl. Methods. Analgesic activity was assessed by tail-immersion test in rats. Results. The relative potency was: (±)cis-3-methyl fentanyl (8)  gt  (±)trans-3-methyl fentanyl (2) $ (±)cis-3-ethyl fentanyl (1.5)  gt  fentanyl (1) $ (±)trans-3-ethyl fentanyl (0.9)  gt  (±)cis-3-butyl fentanyl (0.064) $ (±)trans-3-butyl fentanyl (0.035)  gt  (±)cis-3-benzyl fentanyl (0.008) $ (±)trans-3-benzyl fentanyl (0.0055). (±)Cis-3-iso-propyl fentanyl, and (±)cis-3-phenethyl fentanyl are inactive in doses up to 5 mg/kg. The duration of action (ED99) was: (±)cis-3-methyl fentanyl (90 min)  gt  (±)trans-3-methyl fentanyl (40 min) # (±)cis-3-ethyl fentanyl (60 min) $ (±)trans-3-ethyl fentanyl (40 min) # fentanyl (50 min) = (±)cis-3-butyl fentanyl (50 min) = (±)trans-3-butyl fentanyl (50 min) = (±)cis-3-benzyl fentanyl (50 min) = (±)trans-3-benzyl fentanyl (50 min). Symbols  gt  and  lt  denotes p lt 0.05. Conclusion. It is concluded that the analgesic potency of 3-alkyl fentanyl analogues is influenced by the steric factor (voluminosity of the group at the position 3 of the piperidine ring and the cis/trans isomerism). Otherwise, with the exception of 3-methyl fentanyl, the duration of action of 3-alkyl fentanyl analogues is not significantly affected by the stereochemistry.
AB  - Uvod. Fentanil pripada grupi sintetskih opioidnih analgetika, 4-anilidopiperidina. Karakteriše ga visoka potentnost, brz početak i kratko trajanje dejstva. Do sada je sintetisan veliki broj analoga fentanila, kako u cilju određivanja odnosa strukture i farmakološke aktivnosti, tako i u cilju pronalaženja novog klinički korisnog analgetika. Cilj rada. U studiji su ispitivana analgetska dejstva novosintetisanih 3-alkil analoga fentanila i poređena sa fentanilom. Metod rada. Merenje analgetskog dejstva ispitivanih jedinjenja vršeno je uz pomoć testa potapanja repa pacova u toplu vodu. Rezultati. Relativna jačina jedinjenja iznosila je: (±)cis-3-metil fentanil (8)  gt  (±)trans-3-metil fentanil (2) $ (±)cis-3-etil fentanil (1,5)  gt  fentanil (1) $ (±)trans-3-etil fentanil (0,9)  gt  (±)cis-3-butil fentanil (0,064) $ (±)trans-3-butil fentanil (0,035)  gt  (±)cis-3-benzil fentanil (0,008) $ (±)trans-3-benzil fentanil (0,0055). (±)Cis-3-izopropil fentanil i (±)cis-3-fenetil fentanil nisu ispoljili dejstvo u dozama do 5 mg/kg. Dužina dejstva (ED99) iznosila je: (±)cis-3-metil fentanil (90 min)  gt  (±)trans-3-metil fentanil (40 min) # (±)cis-3-etil fentanil (60 min) $ (±)trans-3-etil fentanil (40 min) # fentanil (50 min) = (±)cis-3-butil fentanil (50 min) = (±)trans-3-butil fentanil (50 min) = (±)cis-3-benzil fentanil (50 min) = (±)trans-3-benzil fentanil (50 min). Oznake  gt  i  lt  označavaju P lt 0.05. Zaključak Zaključeno je da na analgetsku jačinu 3-alkil analoga fentanila utiče sterni faktor (voluminoznost grupe na položaju 3 piperidinskog prstena i cis/trans izomerizam). Inače, uz izuzetak 3-metil fentanila, stereohemija ne utiče značajno na dužinu dejstva 3-alkil analoga fentanila.
T2  - Engrami
T1  - 3-alkyl fentanyl analogues: Structure-activity-relationship study
T1  - 3-alkil analozi fentanila - studija odnosa strukture i aktivnost
VL  - 34
IS  - 3
SP  - 15
EP  - 26
UR  - https://hdl.handle.net/21.15107/rcub_cherry_140
ER  - 

@article{
author = "Vučković, Sonja M. and Savić-Vujović, Katarina and Srebro, Dragana and Ivanović, Milovan and Došen-Mićović, Ljiljana and Stojanović, Radan and Prostran, Milica",
year = "2012",
abstract = "Introduction. Fentanyl belongs to 4-anilidopiperidine class of synthetic opioid analgesics. It is characterized by high potency, rapid onset and short duration of action. A large number of fentanyl analogues have been synthesized so far, both to establish the structure-activity-relationship (SAR) and to find novel, clinically useful analgesic drugs. Objective. In this study, newly synthesized 3-alkyl fentanyl analogues were examined for analgesic activity and compared with fentanyl. Methods. Analgesic activity was assessed by tail-immersion test in rats. Results. The relative potency was: (±)cis-3-methyl fentanyl (8)  gt  (±)trans-3-methyl fentanyl (2) $ (±)cis-3-ethyl fentanyl (1.5)  gt  fentanyl (1) $ (±)trans-3-ethyl fentanyl (0.9)  gt  (±)cis-3-butyl fentanyl (0.064) $ (±)trans-3-butyl fentanyl (0.035)  gt  (±)cis-3-benzyl fentanyl (0.008) $ (±)trans-3-benzyl fentanyl (0.0055). (±)Cis-3-iso-propyl fentanyl, and (±)cis-3-phenethyl fentanyl are inactive in doses up to 5 mg/kg. The duration of action (ED99) was: (±)cis-3-methyl fentanyl (90 min)  gt  (±)trans-3-methyl fentanyl (40 min) # (±)cis-3-ethyl fentanyl (60 min) $ (±)trans-3-ethyl fentanyl (40 min) # fentanyl (50 min) = (±)cis-3-butyl fentanyl (50 min) = (±)trans-3-butyl fentanyl (50 min) = (±)cis-3-benzyl fentanyl (50 min) = (±)trans-3-benzyl fentanyl (50 min). Symbols  gt  and  lt  denotes p lt 0.05. Conclusion. It is concluded that the analgesic potency of 3-alkyl fentanyl analogues is influenced by the steric factor (voluminosity of the group at the position 3 of the piperidine ring and the cis/trans isomerism). Otherwise, with the exception of 3-methyl fentanyl, the duration of action of 3-alkyl fentanyl analogues is not significantly affected by the stereochemistry., Uvod. Fentanil pripada grupi sintetskih opioidnih analgetika, 4-anilidopiperidina. Karakteriše ga visoka potentnost, brz početak i kratko trajanje dejstva. Do sada je sintetisan veliki broj analoga fentanila, kako u cilju određivanja odnosa strukture i farmakološke aktivnosti, tako i u cilju pronalaženja novog klinički korisnog analgetika. Cilj rada. U studiji su ispitivana analgetska dejstva novosintetisanih 3-alkil analoga fentanila i poređena sa fentanilom. Metod rada. Merenje analgetskog dejstva ispitivanih jedinjenja vršeno je uz pomoć testa potapanja repa pacova u toplu vodu. Rezultati. Relativna jačina jedinjenja iznosila je: (±)cis-3-metil fentanil (8)  gt  (±)trans-3-metil fentanil (2) $ (±)cis-3-etil fentanil (1,5)  gt  fentanil (1) $ (±)trans-3-etil fentanil (0,9)  gt  (±)cis-3-butil fentanil (0,064) $ (±)trans-3-butil fentanil (0,035)  gt  (±)cis-3-benzil fentanil (0,008) $ (±)trans-3-benzil fentanil (0,0055). (±)Cis-3-izopropil fentanil i (±)cis-3-fenetil fentanil nisu ispoljili dejstvo u dozama do 5 mg/kg. Dužina dejstva (ED99) iznosila je: (±)cis-3-metil fentanil (90 min)  gt  (±)trans-3-metil fentanil (40 min) # (±)cis-3-etil fentanil (60 min) $ (±)trans-3-etil fentanil (40 min) # fentanil (50 min) = (±)cis-3-butil fentanil (50 min) = (±)trans-3-butil fentanil (50 min) = (±)cis-3-benzil fentanil (50 min) = (±)trans-3-benzil fentanil (50 min). Oznake  gt  i  lt  označavaju P lt 0.05. Zaključak Zaključeno je da na analgetsku jačinu 3-alkil analoga fentanila utiče sterni faktor (voluminoznost grupe na položaju 3 piperidinskog prstena i cis/trans izomerizam). Inače, uz izuzetak 3-metil fentanila, stereohemija ne utiče značajno na dužinu dejstva 3-alkil analoga fentanila.",
journal = "Engrami",
title = "3-alkyl fentanyl analogues: Structure-activity-relationship study, 3-alkil analozi fentanila - studija odnosa strukture i aktivnost",
volume = "34",
number = "3",
pages = "15-26",
url = "https://hdl.handle.net/21.15107/rcub_cherry_140"
}

Vučković, S. M., Savić-Vujović, K., Srebro, D., Ivanović, M., Došen-Mićović, L., Stojanović, R.,& Prostran, M.. (2012). 3-alkyl fentanyl analogues: Structure-activity-relationship study. in Engrami, 34(3), 15-26.
https://hdl.handle.net/21.15107/rcub_cherry_140

Vučković SM, Savić-Vujović K, Srebro D, Ivanović M, Došen-Mićović L, Stojanović R, Prostran M. 3-alkyl fentanyl analogues: Structure-activity-relationship study. in Engrami. 2012;34(3):15-26.
https://hdl.handle.net/21.15107/rcub_cherry_140 .

Vučković, Sonja M., Savić-Vujović, Katarina, Srebro, Dragana, Ivanović, Milovan, Došen-Mićović, Ljiljana, Stojanović, Radan, Prostran, Milica, "3-alkyl fentanyl analogues: Structure-activity-relationship study" in Engrami, 34, no. 3 (2012):15-26,
https://hdl.handle.net/21.15107/rcub_cherry_140 .

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 . .

TY  - JOUR
AU  - Vuckovic, S.
AU  - Prostran, M.
AU  - Ivanović, Milovan
AU  - Došen-Mićović, Ljiljana
AU  - Savic Vujovic, K.
AU  - Vucetic, C.
AU  - Kadija, M.
AU  - Mikovic, Z.
PY  - 2011
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/106
AB  - 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 dosedependent manner. The relative order of antinociceptive potency was similar to motor impairment potency, as well as lethality: F  gt  C  gt  T. Naloxone hydrochloride (1 mg/kg; sc) abolished all the effects observed, suggesting that they are mediated via opioid receptors, most probably of μ 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. © 2011 by the authors.
T2  - Pharmaceuticals
T1  - Pharmacological evaluation of 3-carbomethoxy fentanyl in mice
VL  - 4
IS  - 2
SP  - 233
EP  - 243
DO  - 10.3390/ph4020233
ER  - 

@article{
author = "Vuckovic, S. and Prostran, M. and Ivanović, Milovan and Došen-Mićović, Ljiljana and Savic Vujovic, K. and Vucetic, C. and Kadija, M. and Mikovic, Z.",
year = "2011",
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 dosedependent manner. The relative order of antinociceptive potency was similar to motor impairment potency, as well as lethality: F  gt  C  gt  T. Naloxone hydrochloride (1 mg/kg; sc) abolished all the effects observed, suggesting that they are mediated via opioid receptors, most probably of μ 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. © 2011 by the authors.",
journal = "Pharmaceuticals",
title = "Pharmacological evaluation of 3-carbomethoxy fentanyl in mice",
volume = "4",
number = "2",
pages = "233-243",
doi = "10.3390/ph4020233"
}

Vuckovic, S., Prostran, M., Ivanović, M., Došen-Mićović, L., Savic Vujovic, K., Vucetic, C., Kadija, M.,& Mikovic, Z.. (2011). Pharmacological evaluation of 3-carbomethoxy fentanyl in mice. in Pharmaceuticals, 4(2), 233-243.
https://doi.org/10.3390/ph4020233

Vuckovic S, Prostran M, Ivanović M, Došen-Mićović L, Savic Vujovic K, Vucetic C, Kadija M, Mikovic Z. Pharmacological evaluation of 3-carbomethoxy fentanyl in mice. in Pharmaceuticals. 2011;4(2):233-243.
doi:10.3390/ph4020233 .

Vuckovic, S., Prostran, M., Ivanović, Milovan, Došen-Mićović, Ljiljana, Savic Vujovic, K., Vucetic, C., Kadija, M., Mikovic, Z., "Pharmacological evaluation of 3-carbomethoxy fentanyl in mice" in Pharmaceuticals, 4, no. 2 (2011):233-243,
https://doi.org/10.3390/ph4020233 . .