Ondansetron (ZOFRAN®) is a selective 5-HT3 receptor antagonist. It is effective in the treatment of nausea and vomiting caused by radiotherapy, anesthesia, surgery or cytotoxic chemotherapy drugs, including cisplatin, and has reported anxiolytic and neuroleptic properties. While its mechanism of action has not been fully characterized, ondansetron is not a dopamine-receptor antagonist. It is not certain whether ondansetron's antiemetic action is mediated centrally, peripherally, or in both sites. However, cytotoxic chemotherapy appears to be associated with release of serotonin from the enterochromaffin cells of the small intestine. The released serotonin may stimulate the vagal afferents through the 5-HT3 receptors and initiate the vomiting reflex.

Perphenazine is a relatively high potency phenothiazine that blocks dopamine 2 receptors predominantly, but also may possess antagonist actions at histamine 1 and cholinergic M1 and alpha 1 adrenergic receptors in the vomiting center leading to reduced nausea and vomiting. The drug was approved by FDA for the treatment of schizophrenia and control of severe nausea and vomiting (either alone or in combination with amitriptyline hydrochloride). Perphenazine is extensively hepatic to metabolites via sulfoxidation, hydroxylation, dealkylation, and glucuronidation; primarily metabolized by CYP2D6 to N-dealkylated perphenazine, perphenazine sulfoxide, and 7-hydroxyperphenazine (active metabolite with 70% of the activity of perphenazine) and excreted in the urine and feces.

Prochlorperazine is a piperazine phenothiazine antipsychotic which block postsynaptic mesolimbic dopaminergic receptors in the brain and has antiemetic effects by its antagonist actions in the D2 dopamine receptors in the chemoreceptor trigger zone. It also exhibits alpha-adrenergic blocking effect on α1 receptros and may depress the release of hypothalamic and hypophyseal hormones. Prochlorperazine is used for the control of severe nausea and vomiting, for the treatment of schizophrenia. Prochlorperazine is effective for the short-term treatment of generalized non-psychotic anxiety. Prochlorperazine may be an effective treatment of acute headaches and refractory chronic daily headache.

Benzquinamide also known as BZQ; Emete-con, Emetico, is an antiemetic drug, which was discontinued. That drug was used to prevent and treat nausea and vomiting associated with anesthesia and surgery, administered intramuscularly or intravenously. The mechanism of action is not known, but was made predictions which shown, that in spite of benzquinamide did bind to the α2A, α2B, and α2C adrenergic receptors (α2-AR). It was known, that this activity may partially explain the anxiolytic activity effect of the drug. But the dopamine D2 receptor, which by ligand-set similarity resembles α2-AR is an accepted target for emesis. Then benzquinamide was tested towards to the D2, D3, and D4 receptors. Notwithstanding the fact that the α2-AR values are lower than the D2 values, it was predicted, that D2 activity may be the most relevant for emesis.

Levomepromazine (also known as methotrimeprazine) is a phenothiazine neuroleptic drug. It is sold in many countries under the generic name (levomepromazine) or under brand names such as Nozinan, Detenler and many more. Levomepromazine is an antipsychotic drug is commonly used as an antiemetic to alleviate nausea and vomiting in palliative care settings particularly in terminal illness. Levomepromazine is a phenothiazine with pharmacological activity similar to that of both chlorpromazine and promethazine. It has the histamine-antagonist properties of the antihistamines together with central nervous system effects resembling those of chlorpromazine. Levomepromazine's antipsychotic effect is largely due to its antagonism of dopamine receptors in the brain. In addition, it can block 5HT2 receptors and some others, like histamine, serotonin.

Thiethylperazine is a antiemetic, which was used for the treatment of nausea and vomiting in patients undergoing radiotherapy, chemotherapy or as a postoperative care. Thiethylperazine exerts its therapeutic effect by blocking dopamine receptors in brain. The drug is capable of potentiating CNS depressants as well as atropine.

Fabesetron is a dual 5HT3 and 5HT4 receptors antagonist that was developed in Japan for the treatment of chemotherapy-induced emesis and gastrointestinal disorders. The development of the drug was terminated in phase II.

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.

Prifinium bromide is antimuscarinic drug, which has antispasmodic, antiemetic effect. Prifinium bromideis approved for pain relief in Russia, Indonesia, Iraq, Tunisia and other countries.

Indisetron dihydrochloride (N-3389) was approved by Pharmaceuticals and Medical Devices Agency of Japan (PMDA) on January 29, 2004. It was co-developed and co-marketed as Sinseron by Kyorin & Yakult Honsha in Japan. Indisetron is a dual serotonin 5-HT3 and 5-HT4 receptor antagonist. It is indicated for the treatment of prophylaxis of chemotherapy-induced nausea and vomiting, it’s administered once daily. Indisetron is metabolized in the liver, and CYP1A1, CYP2C9, CYP2D6, and CYP3A4 are involved in its metabolism. However, indisetron is unlikely to cause drug interactions at clinical doses because the effective plasma concentrations are lower than those necessary for inhibiting the metabolic enzymes. No drug interaction has been reported. Indisetron antagonizes 5-HT4 receptors, as well as 5-HT3 receptors, and this characteristic is expected to contribute to its clinical efficacy.