TY - JOUR
T1 - Coadministration of tramadol and tizanidine in an experimental acute pain model in rat
AU - Beltrán-Villalobos, Karla Lizet
AU - Ramírez-Marín, Pamela Monserrat
AU - Cruz, Carlos Alberto Zúñiga
AU - Déciga-Campos, Myrna
N1 - Publisher Copyright:
© 2014 Wiley Periodicals, Inc.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - (Table Presented) The use of drug combinations to achieve a desired effect is a common practice in pharmacological reaserch and in clinical practice. The present study was designed to evaluate the potential synergistic antinociceptive interactions between tizanidine, an α-2-adrenoceptor agonist and tramadol on formalin-induced nociception in rat using isobolographic analyses. Tramadol (0.1-100 μg/paw) and tizanidine (0.01-10 μg/paw) were injected into the paw prior to formalin injection (1%). Both drugs produced a dose-dependent antinociceptive effect. The EC50 values were estimated for individual drugs, and isobolograms were constructed. Tizanidine (EC50 = 0.125 ± 0.026 μg) was more potent than tramadol (EC50 = 16.45 ± 6.4 μg). The combination of tramadol-tizanidine at fixed ratios of 1:1 (EC50exp = 67.43 ± 11 μg; EC50teo = 8.28 ± 3.2 μg) and 3:1 (EC50exp = 31.25 ± 9.49 μg; CE50teo = 12.36 ± 4.8 μg) generated subadditivity (antagonism). On the basis of the current preclinical data, the pharmacological profile of the combination of tramadol-tizanidine produced antagonism. Thus, the utmost caution is required during the use of this combination in clinical practice, due to their antagonistic interaction.
AB - (Table Presented) The use of drug combinations to achieve a desired effect is a common practice in pharmacological reaserch and in clinical practice. The present study was designed to evaluate the potential synergistic antinociceptive interactions between tizanidine, an α-2-adrenoceptor agonist and tramadol on formalin-induced nociception in rat using isobolographic analyses. Tramadol (0.1-100 μg/paw) and tizanidine (0.01-10 μg/paw) were injected into the paw prior to formalin injection (1%). Both drugs produced a dose-dependent antinociceptive effect. The EC50 values were estimated for individual drugs, and isobolograms were constructed. Tizanidine (EC50 = 0.125 ± 0.026 μg) was more potent than tramadol (EC50 = 16.45 ± 6.4 μg). The combination of tramadol-tizanidine at fixed ratios of 1:1 (EC50exp = 67.43 ± 11 μg; EC50teo = 8.28 ± 3.2 μg) and 3:1 (EC50exp = 31.25 ± 9.49 μg; CE50teo = 12.36 ± 4.8 μg) generated subadditivity (antagonism). On the basis of the current preclinical data, the pharmacological profile of the combination of tramadol-tizanidine produced antagonism. Thus, the utmost caution is required during the use of this combination in clinical practice, due to their antagonistic interaction.
KW - Antagonism
KW - Antinocception
KW - Nociception
KW - Tizanidine
KW - Tramadol
UR - http://www.scopus.com/inward/record.url?scp=84919668365&partnerID=8YFLogxK
U2 - 10.1002/ddr.21229
DO - 10.1002/ddr.21229
M3 - Artículo
C2 - 25328066
SN - 0272-4391
VL - 75
SP - 473
EP - 478
JO - Drug Development Research
JF - Drug Development Research
IS - 8
ER -