Evaluation the combination of chlorpheniramine and tramadol at a level of thermal and visceral antinociceptive in a mouse acute pain model

Abstract

The possible benefits of employing combination treatment include the ability to increase antinociceptive effects while minimizing the occurrence of unfavorable side effects. As a result, they are combining drugs that provide analgesic synergism allowing for a reduction in needed dosage as well as lowering the occurrence of unwanted side effects. In the current study, we evaluated quantitatively and qualitatively the type of drug interaction between tramadol (a typical opioid analgesic) and chlorpheniramine (an H1-antagonist) at the level of thermal (hot plate) and visceral (writhing reflex) nociceptive stimuli in mice model. The 50% antinociceptive effective dose (ED50) of intraperitoneal administration for tramadol and chlorpheniramine was 12 and 18.4 mg/kg respectively, using the up and down approach and hot plate apparatus. The treated animals showed signs of sedation and immobility. At 0.5:0.5 and 1:1 ED50 ratios of each, the kind of pharmacological interaction between the two medications was synergism at the level of acute antinociceptive impact, using hot plate apparatus and isobolographic analysis. The reduction in ED50 value was significant for tramadol and chlorpheniramine by 58.8 and 58.8 % at 0.5:0.5 ratio while 53.5 and 53.5 % at 1:1 ratio respectively. The synergistic interaction between the two drugs was also confirmed using the double ED50 dose of each drug as simultaneously i.p. injected of these doses producing a synergism antinociceptive effect at visceral (writhing reflex) test. Which represented as prevent 100% writhing induced by i.p. injection of acetic acid compared to the control group and that with each drug alone at the same double doses. The present results concluded that simultaneous injection of tramadol and chlorpheniramine produced synergism, a potent and safe antinociceptive effect even at low doses which may be clinically useful in treating pain in the veterinary clinic.

Keywords

• antinociceptive
• chlorpheniramine
• hot plate
• tramadol
• writhing reflex