There was no sedation, overt stimulation of activity, salivation or diarrhoea at any dose of loperamide or with any antagonist combination. Prior to each bout of emesis, the animals exhibited characteristic licking, backing and burrowing, as has been reported with other emetic stimuli . Effect of rechallenge with loperamide on initial loperamide induced emesis On re exposure to loperamide 0.5 mg kg , 60 min after administration of the initial dose of loperamide , there were no more emetic episodes, i.e. it was not possible to induce an additional emetic response Effect of opiate receptor antagonists on the response to loperamide Naioxone or its analogues were injected subcutaneously at a dose of 1 mg kg, 5 min before loperamide and the animals were observed for 5 hr. They were injected 5 min before loperamide because of the expected short half life of naloxone . The period of observation was extended to 5 hr, based on preliminary unpublished experiments, so that any residual effect of loperamide, occurring after the effects of antagonists had subsided, could be observed.
Although there was no decrease in total retches or total vomits after naloxone {n 6 , the mean latency to retch was increased to 98.3 8.9 min , with a minimum of 61.3 and a maximum of 143.1 min . In another group of 4 animals it was seen that naloxone alone did not cause any emesis. It appears that Wortmannin kinase inhibitor naloxone merely shifted the emetic response to loperamide by preventing emesis for the first 60 min. Naloxone also increased the duration of the response. Naloxone methiodide also increased the latency to retch similarly , with a decrease in total retches and total vomits . Naloxonazine, however, prevented all emetic responses to loperamide . E ect of rechallenge with naioxone on loperamideinduced emesis In a separate group of 4 animals, treated with naloxone and loperamide as above, rechallenge with natoxone after the first vomit, prevented any further retching or vomiting within 10 min and there was no reappearance of emesis for the rest of the period of observation .
E ect of Shydroxytryptamine, receptor antagonists or a hydroxytryptamine depletor on the response to ioperamide Ondansetron or granisetron were both without significant effect on the emesis. In a preliminary study, in two animals, para chlorophenylalanine , a depletor of serotonin, administered purchase IOX2 at a dose of 180mg kg for 3 days prior to challenge with loperamide, did not modify the response to loperamide. 6 0 8b 1 3 120 140 160 160 200 220 240 Time c I1 Loperamide naloxona 60 60 100 120 140 160 160 200 220 240 Time Fig. 3. Profile of retches or vomits, after injection of loperamide and naioxone , as described in the text. The x and y axes are as in fegend for Fig. 2 . Bizarre But Nonetheless , Possible Rucaparib Tactics