A series of pyrrolizidine esters, amides, and ureas was prepared and tested for 5-HT(4) and 5-HT(3) receptor binding, 5-HT(4) receptor agonism in the rat tunica muscularis mucosae (TMM) assay, and for 5-HT(3) receptor-mediated functional antagonism in the Bezold-Jarisch reflex assay. Several pyrrolizidine derivatives were identified with high affinity for… (More)
Azaadamantanone 1 was converted to a series of aminoazaadamantane benzamides 9a-d, which were profiled for serotonin receptor activity. Aminomethylazaadamantane SC-54750 is a potent 5-HT(4) agonist and 5-HT(3) antagonist with in vivo efficacy in gastroparesis models and also inhibits cisplatin-induced emesis.
The immunomodulator, imiquimod, has been shown to have antiviral and antitumor properties in animal models. It also has been reported to alter cytokine levels in both animals and humans. However, because imiquimod appeared to be emetic, studies were conducted to determine the degree of sensitivity, and the pathways involved. Subcutaneous administration of >… (More)
Five Long-Evans hooded rats were trained to lever press according to fixed-ratio 5 reinforcement schedules for 0.06 ml dipper deliveries of 8% w/v ethanol during daily (M-F) 0.5-h experimental sessions. After ethanol self-administration was established, doses of the serotonin 5-HT3 antagonists, ondansetron (0.03-3.0 mg/kg), granisetron (0.01-1.0 mg/kg), and… (More)
5-HT3 receptor antagonists may have both antiemetic and gastric and intestinal motility stimulating properties, but they differ in their relative potencies and efficacies for these two activities. Since the 5-HT3 receptor is present on enteric neurons, intracellular recordings of myenteric neuronal transmembrane potential were used to assess the actions of… (More)