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Droxytryptamine (5-HT; serotonin) 5-HT3 receptor is an excitatory ligandgated ion channel expressed in for example the brain and the gastrointestinal tract. CSTI-300 as a selective, high affinity 5-HT3 receptor partial agonist. CSTI-300 was examined alongside the selective 5-HT3 receptor antagonist alosetron (which is also currently marketed as a therapeutic for IBS-d). Sub-cutaneous application of 5-hydroxytryptophan (5-HTP; 10 mg/kg) markedly increased the rat¡¯s sensitivity to abdominal contractions. CSTI-300 and Alosetron displayed similar efficacy in a rodent in vivo model of IBS-d, measured by a reduction in colonic sensitivity. The experiments (Rat colon distension model of IBS-d) were carried out by Medicilon. The protocol complied with and was approved by the Institutional Animal Care and Use Committee and Medicilon is accredited by the NIH Office of laboratory Animal Welfare (OLAW) and AAALAC. Experiments (dog behavioural and emesis model) were performed by Medicilon. The protocol for the dog behavioural and emesis model complied with and was approved by the Institutional Animal Care and Use Committee.