SYNERGISTIC EFFECS OT THE DOXEPIN-CANDESARTAN
COMBINATION ON THE THERMOALGESIC SENSIBILITY IN MICE
DANIELA CARMEN ABABEI1, SORIN BEȘCHEA CHIRIAC5*, WALTHER BILD2,3, CARMEN SOLCAN5, ANDREI LUCA4, RĂZVAN NICOLAE RUSU1, DELIA BULEA1, VERONICA BILD1,2,4
1“Grigore T. Popa” University of Medicine and Pharmacy, Faculty of Pharmacy, Pharmacodynamics and Clinical
Pharmacy Department, Iași, Romania
2Center of Biomedical Research of the Romanian Academy, Iași, Romania
3”Grigore T. Popa” University of Medicine and Pharmacy, Faculty of Medicine, Physiology Department, Iași, Romania
4”Grigore T. Popa” University of Medicine and Pharmacy, CEMEX Department, Iași, Romania
5”Ion Ionescu de la Brad” University of Agricultural Sciences and Veterinary Medicine, Faculty of Veterinary Medicine,
Iași, Romania
*corresponding author: sbeschea@yahoo.com
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Abstract:
Given the multitude of neuromodulators involved in the generation and transmission of pain, two therapeutic agents with
different action mechanisms (an antidepressant - doxepin and an angiotensin-AT1 receptor blocker - candesartan) have been
associated in this study. None of the substances is used exclusively as analgesic, but increasingly as adjuvants. The hot-plate
test at 52.5°C was used as a study method of the thermal stimulation nociception. For the analysis of the interaction, the
additive composite method was used. The study was performed on Swiss mice weighing 18 - 22 grams, which received oral
administration of the drugs, either single or combined work-ups. The data obtained demonstrated a synergic type interaction
(Zadd = 7.74 ± 0.92, Zmix = 1.82 ± 0.36, p1 = 0.931, p2 = 0.069, = 0.5, γ = 0.282, Tc = 6.20, Tt = 3.79, Fc = 15.30, Ft = 5.14,
p < 0.001) between doxepin and candesartan. Both substances exhibited antinociceptive effects per se, and the fixed-ratio
combination proved to be synergistic.

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