Zacopride is a potent antagonist at the 5-HT3 receptor and an agonist at the 5-HT4 receptor with antiemetic, anxiolytic and nootropic effects in animal models. Zacopride also has pro-respiratory effects, both reducing sleep apnea and reversing opioid-induced respiratory depression in animal studies. Zacopride has been tested in clinical trials for the treatment of schizophrenia but was found unsuccessful.

Azasetron is an antiemetic drug. It acts as serotonin 3 receptor antagonist. It is currently used to prevent nausea and vomiting caused by cancer chemotherapy (including cisplatin chemotherapy). Also it was demonstrated that azasetron has potent antimitogenic and apoptotic effect on cancer cell line. It was preclinically tested to treat cocaine abuse.

OXYPENDYL, an azaphenothiazine derivative, is an antiemetic drug. It may also possess neuroleptic potency.

Ramosetron (INN) is a serotonin 5-HT3 receptor antagonist for the treatment of nausea, vomiting. And "diarrhea-predominant irritable bowel syndrome in males" (IBS-D). Ramosetron is licensed for use in India, Japan (Iribo) and selected Southeast Asian countries. In animal studies, ramosetron reduced defecation induced by corticotrophin-releasing hormone and had inhibitory effects on colonic nociception. In two randomized controlled studies including 957 patients with IBS-D, ramosetron increased monthly responder rates of patient-reported global assessment of IBS symptom relief compared with placebo. Ramosetron was also as effective as mebeverine in male patients with IBS-D. In a recent randomized controlled trial with 343 male patients with IBS-D, ramosetron has proved effective in improving stool consistency, relieving abdominal pain/discomfort, and improving health-related quality of life. Regarding safety, ramosetron is associated with a lower incidence of constipation compared with other 5-HT3 receptor antagonists and has not been associated with ischemic colitis.

Acotiamide (Acofide(®)), an oral first-in-class prokinetic drug, is under global development by Zeria Pharmaceutical Co. Ltd and Astellas Pharma Inc. for the treatment of patients with functional dyspepsia. The drug modulates upper gastrointestinal motility to alleviate abdominal symptoms resulting from hypomotility and delayed gastric emptying. It exerts its activity in the stomach via muscarinic receptor inhibition, resulting in enhanced acetylcholine release and inhibition of acetylcholinesterase activity. Acofide® is launched in Japan for treating functional dyspepsia.

DAU 6215 (Itasetron) is a selective 5-hydroxytryptamine3 (5-HT3) antagonist, which was developed by Boehringer Ingelheim. And was investigated for treatment the nausea and vomiting induced by chemotherapy, it was confirmed that this drug possessed antiemetic properties. Also was discovered, that chronic treatment with itasetron significantly improved retention abilities of the aged rats in this memory test. However, development of itasetron was terminated.

Bromopride is a dopamine D2 receptor blocker. Bromopride exerts is a gastrointestinal prokinetic exploited clinically for the management of motor disorders of the upper gastrointestinal tract, including functional dyspepsia, gastric stasis of various origins and emesis.

Tropisetron (Tropisetron-AFT) is a potent and selective serotonin 3 (5-hydroxytryptamine3; 5-HT3) receptor antagonist with antiemetic properties, probably mediated via antagonism of receptors both at peripheral sites and in the central nervous system. Surgery and treatment with certain substances, including some chemotherapeutic agents, may trigger the release of serotonin from enterochromaffin-like cells in the visceral mucosa and initiate the emesis reflex and its accompanying feeling of nausea. Tropisetron (Tropisetron-AFT) selectively blocks the excitation of the presynaptic 5-HT3 receptors of the peripheral neurons in this reflex, and may exert additional direct actions within the CNS on 5-HT3 receptors mediating the actions of vagal input to the area postrema.

Metopimazine, a phenothiazine derivative, is a dopamine D2 receptor antagonist. It exerts its antiemetic effects via the chemoreceptor trigger zone. Metopimazine showed potent alpha-adrenergic blocking activity, showed histamine H1 antagonism, and induced palpebral ptosis. Metopimazine can occasionally be associated with orthostatic hypotension, which probably relates to its affinity for the α1-adrenoceptor. Therapeutic doses of metopimazine are likely to produce sedation and side-effects related to autonomic blockade. Metopimazine (Vogalene®) is indicated for the prevention and treatment of nausea and vomiting.

Alizapride is a dopamine antagonist with prokinetic and antiemetic effects used in the treatment of nausea and vomiting, including postoperative nausea and vomiting. The anti-emetic action of Alizapride is due to its antagonist activity at D2 receptors in the chemoreceptor trigger zone (CTZ) in the central nervous system (CNS)—this action prevents nausea and vomiting triggered by most stimuli. Structurally similar to metoclopramide and, therefore, shares similar other attributes related to emesis and prokinetics.