TY - JOUR
T1 - Low doses of tizanidine synergize the anti-nociceptive and anti-inflammatory effects of ketorolac or naproxen while reducing of side effects
AU - Patiño-Camacho, Selene I.
AU - Déciga Campos, Myrna
AU - Beltrán-Villalobos, Karla
AU - Castro-Vidal, Dalia A.
AU - Montiel-Ruiz, Rosa M.
AU - Flores-Murrieta, Francisco J.
N1 - Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017
Y1 - 2017
N2 - The aim of the present study was to determine whether tizanidine, an alpha2-adrenoceptor agonist, is able to increase the anti-inflammatory and anti-nociceptive effects of naproxen and ketorolac with a low incidence of gastric injury and spontaneous activity in rats. The anti-inflammatory effect was assayed in a carrageenan test, and oral administration of tizanidine (ED40 =0.94±0.2 mg/kg), naproxen (ED40=3.18±0.4 mg/kg), and ketorolac (ED40=16.4±1.9 mg/kg) showed a dose-dependent effect on inflammation. The anti-nociceptive effect was assayed in the formalin test, and administration of tizanidine (ED40=0.39±0.06 mg/kg, p.o.), naproxen (ED40=33.9±3.9 mg/kg, p.o.) or ketorolac (ED40=6.49±1 mg/kg, p.o.) each showed a dose-dependent anti-nociceptive effect. The effects of combinations of tizanidine/naproxen and tizanidine/ketorolac were determined considering their ED40 at a rate of 1:1. Additionally, the tizanidine/naproxen and tizanidine/ketorolac combinations showed anti-inflammatory and anti-nociceptive effects. The tizanidine/ketorolac combination was more potent than tizanidine/naproxen, in both inflammatory (interaction index=0.03 tizanidine/ketorolac and 0.07 tizanidine/naproxen) and nociceptive (interaction index=0.005 tizanidine/ketorolac and 0.01 tizanidine/naproxen) processes. In both cases, tizanidine improved naproxen and ketorolac gastrointestinal tolerability by 50%. Furthermore, co-administration of tizanidine with naproxen or ketorolac did not modify the spontaneous activity in the same way as individual tizanidine administration. Considering that tizanidine increases the anti-inflammatory and anti-nociceptive effects of naproxen or ketorolac, with an increase in gastric tolerability, tizanidine could provide therapeutic advantages in the clinical treatment of inflammation and pain.
AB - The aim of the present study was to determine whether tizanidine, an alpha2-adrenoceptor agonist, is able to increase the anti-inflammatory and anti-nociceptive effects of naproxen and ketorolac with a low incidence of gastric injury and spontaneous activity in rats. The anti-inflammatory effect was assayed in a carrageenan test, and oral administration of tizanidine (ED40 =0.94±0.2 mg/kg), naproxen (ED40=3.18±0.4 mg/kg), and ketorolac (ED40=16.4±1.9 mg/kg) showed a dose-dependent effect on inflammation. The anti-nociceptive effect was assayed in the formalin test, and administration of tizanidine (ED40=0.39±0.06 mg/kg, p.o.), naproxen (ED40=33.9±3.9 mg/kg, p.o.) or ketorolac (ED40=6.49±1 mg/kg, p.o.) each showed a dose-dependent anti-nociceptive effect. The effects of combinations of tizanidine/naproxen and tizanidine/ketorolac were determined considering their ED40 at a rate of 1:1. Additionally, the tizanidine/naproxen and tizanidine/ketorolac combinations showed anti-inflammatory and anti-nociceptive effects. The tizanidine/ketorolac combination was more potent than tizanidine/naproxen, in both inflammatory (interaction index=0.03 tizanidine/ketorolac and 0.07 tizanidine/naproxen) and nociceptive (interaction index=0.005 tizanidine/ketorolac and 0.01 tizanidine/naproxen) processes. In both cases, tizanidine improved naproxen and ketorolac gastrointestinal tolerability by 50%. Furthermore, co-administration of tizanidine with naproxen or ketorolac did not modify the spontaneous activity in the same way as individual tizanidine administration. Considering that tizanidine increases the anti-inflammatory and anti-nociceptive effects of naproxen or ketorolac, with an increase in gastric tolerability, tizanidine could provide therapeutic advantages in the clinical treatment of inflammation and pain.
KW - Anti-inflammatory effect
KW - Anti-nociception
KW - Combination
KW - Ketorolac
KW - Naproxen
KW - Synergism
KW - Tizanidine
UR - http://www.scopus.com/inward/record.url?scp=85016029564&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2017.03.021
DO - 10.1016/j.ejphar.2017.03.021
M3 - Artículo
C2 - 28315341
AN - SCOPUS:85016029564
SN - 0014-2999
VL - 805
SP - 51
EP - 57
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
ER -