ABSTRACT
The effects of trimebutine, a peripheral opiate agonist, were investigated on the development of paw oedema by carrageenan, on visceral nociception caused by i.p. injection of acetic acid, on gastric mucosal injury induced by indomethacin and on gastric acid secretion in rats. I.p administration of trimebutine at 30, 60 or 120 mg/kg, at 30-min pretreatment, decreased paw oedema caused by carrageenan injection by 18.2-21.6%, 27.3%- 22.8% and 33.6%- 29.3%, respectively, with maximal inhibition being observed at 1-2 hr post-carrageenan. In addition, trimebutine in doses of 30, 60 or 120 mg/kg [i.p.] 30 mm after carrageenan challenge inhibited the paw oedema response by -21.2, -17%, 22.3, -21.2% and -33.1, -30% at 3 and 4 hr post-carrageenan, respectively. Trimebutine [60 mg/kg] co-administered with meloxicam [3.8 mg/kg], indomethacin [18 mg/kg] or dexamethasone [0.2 mg/kg] resulted in an additive effect. Abdominal writhes induced by i.p. injection of acetic acid were effectively inhibited by trimebutine. The drug enhanced the development of lesions by indomethacin in a dose-dependent manner. In anaesthetised rats, trimebutine caused dose-dependent inhibition of gastric acid secretion. Results indicate that trimebutine possesses anti-inflammatory properties in addition to its visceral analgesic effects. The drug likely exacerbates gastric mucosal lesions by non-steroidal anti inflammatory drugs and consequently their concurrent administration is not advisable