Opioid mediated anti-nociceptive effect of domperidone and cisapride in mice

To study the anti-nociceptive effect of domperidone and cisapride in mice.

Initially, the effect of these drugs on motor activity was tested using rotarod. The anti-nociception was tested using chemical and mechanical assay. In the chemical assay, the number of abdominal constrictions either in the saline treated animals or in the domperidone/cisapride (1, 5, or 10 mg/kg either po or ip) treated mice, were recorded for a period of 30 min after acetic acid challenge (10 mL/kg, of 0.6 % acetic acid ip). In the tail clip assay, the time taken by the mouse to make attempts to dislodge the bulldog clamp placed at the tail (reaction time) was recorded with a cut off time of 30 s. The role of opioid pathways was examined by pretreating the animals with naloxone (1 mg/kg, ip) 30 min prior to domperidone and cisapride.

Domperidone and cisapride, both reduced the number of abdominal constrictions when given orally or intraperitoneally. Domperidone (5 mg/kg) inhibited it to the extent of 57.0 % after po and 54.6 % after ip. The inhibition after cisapride (5 mg/kg) was 65.1 % (po) and 71.6 % (ip). Naloxone pretreatment reduced this inhibition (57.0 % vs 10.3 % for domperidone and induced hyperalgesia by antagonizing the inhibition and enhanced analgesia to the extent of 28.4 % for cisapride). The reaction time was increased by domperidone (10 mg/kg, ip) from 1.6 s +/- 1.0 s to 14.8 s +/- 0.5 s and cisapride (10 mg/kg, ip) from 3.3 s +/- 1.0 s to 14.8 s +/- 0.5 s.

Domperidone and cisapride exhibited a significant anti-nociceptive activity after oral as well as intraperitoneal administration. A role for opioid pathways is indicated. Since domperidone is likely to exert less extrapyramidal effects, it can be substituted for metoclopramide, which is now widely used as an analgesic either alone or as an adjuvant.