Study of drug-drug interaction between loperamide and α₂ adrenergic receptor agonists in rodents

To investigate any alteration in antidiarrhoeal activity of loperamide on concomitant administration with α₂ agonists like methyldopa, clonidine or tizanidine in rodents. Diarrhoea was induced in rats by (1) administration of castor oil (1 mL/100 g) or (2) prostaglandin E₂ (100 mcg/kg). Loperamide or α₂ agonists individually or their combinations were administered one hour before induction of diarrhoea in rats. Antimotility effect of these drugs was studied by charcoal meal test in mice. The interaction of loperamide with α₂ agonists was studied in these models. In castor oil and PGE₂ induced diarrhoea loperamide, clonidine, tizanidine significantly inhibited the faecal mass and secretions. Combination of loperamide with clonidine or tizanidine potentiated the antidiarrhoeal effect of loperamide in these models. Methyldopa did not produce any antidiarrhoeal effect when administered alone. On combination with loperamide it inhibited the antidiarrhoeal action of loperamide. In charcoal meal test, the antimotility effect of loperamide was not altered by clonidine or tizanidine co-administration. While combination of methyldopa with loperamide, inhibited the antimotility effect of loperamide. The present study revealed that the antidiarrhoeal effect of loperamide was potentiated by tizanidine and clonidine. However, methyldopa inhibited the antidiarrhoeal effect of loperamide.