Role of alpha 2-adrenoceptors in the local peripheral antinociception by carbamazepine in a rat model of inflammatory mechanical hyperalgesia
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Vučković, Sonja M.Tomić, Maja

Stepanović-Petrović, Radica

Ugrešić, Nenad
Prostran, Milica

Bošković, Bogdan
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The anticonvulsant carbamazepine was recently shown to possess local peripheral antinociceptive properties. In this study, we investigated whether alpha 2-adrenergic receptors are involved in the local peripheral antihyperalgesic effects of carbamazepine and determined the type of interaction between carbamazepine and clonidine, an alpha 2-adrenoceptor agonist. Intraplantar (i.pl.) coadministration of either carbamazepine (100-1000 nmol/paw) or clonidine (1.9-3.7 nmol/paw) with the proinflammatory compound concanavalin A (Con A; 0.8 mg/paw) caused a significant dose- and time-dependent reduction of the difference between the forces exerted by a rat's hind paws in a modified paw-pressure test. The coadministration of 260 and 520 nmol/paw (i.pl.) yohimbine, an alpha 2-adrenoceptor antagonist, with carbamazepine, significantly depressed the local antihyperalgesic effect in a dose- and time-dependent manner whereas yohimbine by itself did not have any effect. The administration of a mixtur...e of carbamazepine and clonidine at fixed dose fractions (114, 112 and 314) of ED50 caused a significant and dose-dependent reduction of Con A-induced hyperalgesia. Isobolographic analysis revealed an additive interaction. These results suggest that alpha 2-adrenoceptors play a role in the local peripheral antihyperalgesic effects of carbamazepine and that local peripheral coadministration of carbamazepine with clonidine results in an additive antihyperalgesic effect.
Keywords:
additive interaction / carbamazepine / clonidine / inflammatory hyperalgesia / isobolographic analysis / local administration / peripheral alpha 2-adrenoceptors / yohimbineSource:
Methods and Findings in Experimental and Clinical Pharmacology, 2007, 29, 10, 689-696Publisher:
- Prous Science, Sa, Barcelona
DOI: 10.1358/mf.2007.29.10.1147773
ISSN: 0379-0355
PubMed: 18200332
WoS: 000252779800005
Scopus: 2-s2.0-39149128222
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PharmacyTY - JOUR AU - Vučković, Sonja M. AU - Tomić, Maja AU - Stepanović-Petrović, Radica AU - Ugrešić, Nenad AU - Prostran, Milica AU - Bošković, Bogdan PY - 2007 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/904 AB - The anticonvulsant carbamazepine was recently shown to possess local peripheral antinociceptive properties. In this study, we investigated whether alpha 2-adrenergic receptors are involved in the local peripheral antihyperalgesic effects of carbamazepine and determined the type of interaction between carbamazepine and clonidine, an alpha 2-adrenoceptor agonist. Intraplantar (i.pl.) coadministration of either carbamazepine (100-1000 nmol/paw) or clonidine (1.9-3.7 nmol/paw) with the proinflammatory compound concanavalin A (Con A; 0.8 mg/paw) caused a significant dose- and time-dependent reduction of the difference between the forces exerted by a rat's hind paws in a modified paw-pressure test. The coadministration of 260 and 520 nmol/paw (i.pl.) yohimbine, an alpha 2-adrenoceptor antagonist, with carbamazepine, significantly depressed the local antihyperalgesic effect in a dose- and time-dependent manner whereas yohimbine by itself did not have any effect. The administration of a mixture of carbamazepine and clonidine at fixed dose fractions (114, 112 and 314) of ED50 caused a significant and dose-dependent reduction of Con A-induced hyperalgesia. Isobolographic analysis revealed an additive interaction. These results suggest that alpha 2-adrenoceptors play a role in the local peripheral antihyperalgesic effects of carbamazepine and that local peripheral coadministration of carbamazepine with clonidine results in an additive antihyperalgesic effect. PB - Prous Science, Sa, Barcelona T2 - Methods and Findings in Experimental and Clinical Pharmacology T1 - Role of alpha 2-adrenoceptors in the local peripheral antinociception by carbamazepine in a rat model of inflammatory mechanical hyperalgesia VL - 29 IS - 10 SP - 689 EP - 696 DO - 10.1358/mf.2007.29.10.1147773 ER -
@article{ author = "Vučković, Sonja M. and Tomić, Maja and Stepanović-Petrović, Radica and Ugrešić, Nenad and Prostran, Milica and Bošković, Bogdan", year = "2007", abstract = "The anticonvulsant carbamazepine was recently shown to possess local peripheral antinociceptive properties. In this study, we investigated whether alpha 2-adrenergic receptors are involved in the local peripheral antihyperalgesic effects of carbamazepine and determined the type of interaction between carbamazepine and clonidine, an alpha 2-adrenoceptor agonist. Intraplantar (i.pl.) coadministration of either carbamazepine (100-1000 nmol/paw) or clonidine (1.9-3.7 nmol/paw) with the proinflammatory compound concanavalin A (Con A; 0.8 mg/paw) caused a significant dose- and time-dependent reduction of the difference between the forces exerted by a rat's hind paws in a modified paw-pressure test. The coadministration of 260 and 520 nmol/paw (i.pl.) yohimbine, an alpha 2-adrenoceptor antagonist, with carbamazepine, significantly depressed the local antihyperalgesic effect in a dose- and time-dependent manner whereas yohimbine by itself did not have any effect. The administration of a mixture of carbamazepine and clonidine at fixed dose fractions (114, 112 and 314) of ED50 caused a significant and dose-dependent reduction of Con A-induced hyperalgesia. Isobolographic analysis revealed an additive interaction. These results suggest that alpha 2-adrenoceptors play a role in the local peripheral antihyperalgesic effects of carbamazepine and that local peripheral coadministration of carbamazepine with clonidine results in an additive antihyperalgesic effect.", publisher = "Prous Science, Sa, Barcelona", journal = "Methods and Findings in Experimental and Clinical Pharmacology", title = "Role of alpha 2-adrenoceptors in the local peripheral antinociception by carbamazepine in a rat model of inflammatory mechanical hyperalgesia", volume = "29", number = "10", pages = "689-696", doi = "10.1358/mf.2007.29.10.1147773" }
Vučković, S. M., Tomić, M., Stepanović-Petrović, R., Ugrešić, N., Prostran, M.,& Bošković, B.. (2007). Role of alpha 2-adrenoceptors in the local peripheral antinociception by carbamazepine in a rat model of inflammatory mechanical hyperalgesia. in Methods and Findings in Experimental and Clinical Pharmacology Prous Science, Sa, Barcelona., 29(10), 689-696. https://doi.org/10.1358/mf.2007.29.10.1147773
Vučković SM, Tomić M, Stepanović-Petrović R, Ugrešić N, Prostran M, Bošković B. Role of alpha 2-adrenoceptors in the local peripheral antinociception by carbamazepine in a rat model of inflammatory mechanical hyperalgesia. in Methods and Findings in Experimental and Clinical Pharmacology. 2007;29(10):689-696. doi:10.1358/mf.2007.29.10.1147773 .
Vučković, Sonja M., Tomić, Maja, Stepanović-Petrović, Radica, Ugrešić, Nenad, Prostran, Milica, Bošković, Bogdan, "Role of alpha 2-adrenoceptors in the local peripheral antinociception by carbamazepine in a rat model of inflammatory mechanical hyperalgesia" in Methods and Findings in Experimental and Clinical Pharmacology, 29, no. 10 (2007):689-696, https://doi.org/10.1358/mf.2007.29.10.1147773 . .