Computer-assisted isobolographic analysis of interaction between diclofenac and neostigmine for antinociceptive activity in experimental animals

Abstract EN

It is well recognized that Nonsteroidal anti-inflammatory drugs (NSAIDs) produce their antinociceptive action through inhibition of cyclooxygenase enzymes.

It has been found that cholinergic agonists are also antinociceptive.

The main objective of the present study was to evaluate the possible interaction between neostigmine and diclofenac in mice by the acetic acid writhing test.

Intraperitoneal administration of neostigmine and diclofenac at different antinociceptive doses allowed to develop dose response curves for each of them and calculation of corresponding ED50s.

The interactions of neostigmine with diclofenac were evaluated by isobolographic analysis after concomitant intraperitoneal administration of both drugs at fixed ratios of their ED50s.

The combinations of both drugs were found synergistic by isobolographic analysis.

Calculation of interaction index a as an alternative method to isobolographic analysis of drug interaction gave the same result of synergistic interaction for antinociception between the two drugs when concurrently given.

The synergistic interaction between neostigmine and diclofenac could be of clinical importance especially in chronic pain through reduction of analgesic doses and .consequently, adverse effects of given analgesics.