Domperidone is a peripherally selective D2 receptor antagonist. It acts as an antiemetic and a prokinetic agent through its effects on the chemoreceptor trigger zone and motor function of the stomach and small intestine. Domperidone was not approved in USA due to risks of cardiac arrhythmias, cardiac arrest, and sudden death, but is available in other countries. However, FDA allows access to Domperidone through an expanded access investigational new drug application (IND) to patients with gastroesophageal reflux disease with upper GI symptoms, gastroparesis, and chronic constipation. As an “off-label” use, domperidone is prescribed to breastfeeding women to enhance their milk production.

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.

Trichlormethine is a nitrogen mustard vesicant that has application in chemical warfare and has been used as a cytostatic alkylating agent in leukemia and lymphoma therapy. Trichlormethine was tested for carcinogenicity by subcutaneous injection in mice and rats. The study in mice was inadequate for evaluation. In rats, trichlormethine induced a high incidence of sarcomas (mostly spindle-cell type) in animals of each sex at the site of subcutaneous injection, as well as a few intestinal adenocarcinomas; neither tumor type was seen in controls. Trichlormethine caused vomiting, anorexia and blood-containing feces in dogs a few hours after a single intravenous injection of 1 mg/kg BW. Decreased peripheral lymphocyte counts were observed in rabbits injected intravenously and in mice injected subcutaneously with trichlormethine. Trichlormethine was tested for carcinogenicity by subcutaneous injection in mice and rats. ln rats, trichlormethine induced a high incidence of sarcomas (mostly spindle-cell type) in animals of each sex at the site of subcutaneous injection, as well as a few intestinal adenocarcinomas; neither tumor type was seen in controls. Trichlormethine is possibly carcinogenic to humans (Group 2B).

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.

Vernakalant is a new antiarrhythmic drug that acts selectively in the atrium, targeting atrial specific channels. Vernakalant is an anti-arrhythmic medicine that acts preferentially in the atria by prolonging atrial refractoriness and by rate-dependently slowing impulse conduction. These anti-fibrillatory actions on refractoriness and conduction are thought to suppress reentry, and are potentiated in the atria during atrial fibrillation. The preferential effects of vernakalant on the atria are postulated to result from its block of currents that are expressed in the atria (e.g., the ultra-rapid delayed rectifier potassium current; and the acetylcholine-activated potassium current), but not in the ventricles, as well as the unique electrophysiologic condition of the fibrillating atria. An oral formulation of vernakalant is in phase II development as a long-term maintenance therapy for patients with atrial fibrillation. An intravenous formulation of vernakalant has been launched in most countries in Europe and Latin America, and in Hong Kong, for the acute conversion of atrial fibrillation. The product has been approved for the acute conversion of atrial fibrillation in South Africa, Iceland, Turkey and is awaiting approval for the same indication in Canada. Phase III development of the IV formulation is ongoing at sites in Asia, and development is currently on hold in the US.

Lidamidine, also known as WHR-1142A and Lidaral, is an alpha2-adrenergic receptor agonist that inhibits intestinal secretion, reduces intestinal transit, and inhibits smooth muscle contraction. Lidamidine hydrochloride is used to treat diarrhoea and other gastrointestinal disorders. Lidamidine’s intestinal antisecretory effects are mediated through the activation of peripheral alpha-2 adrenoceptors. Lidamidine crosses the blood brain barrier poorly and is therefore devoid of the centrally mediated alpha-2 effects that have limited the use of other alpha-2 adrenoceptor agonists in the intestinal tract.