[5] Unlike domperidone however, metopimazine shows no hERG inhibition and hence is expected to have a more favorable cardiovascular profile.

[5] Metopimazine is an approved prescription drug in France under the brand name Vogalene® [8] that has been used for the treatment of nausea and vomiting.

[22] In a randomized, double-blind comparison of ondansetron versus ondansetron plus metopimazine as an antiemetic prophylaxis during platinum-based chemotherapy, metopimazine was administered by IV (24-hour continuous infusion) at 35 mg/m2 followed by 30 mg per orally (PO) 4 times a day (120 mg/day) for 4 days.

However, there was an asymptomatic decrease in standing blood pressure when patients received the combination antiemetic therapy.

[19] In a randomized, double-blind study assessing the efficacy and safety of sublingual metopimazine compared to ondansetron in chemotherapy-induced delayed emesis, patients received either 45 mg/day of metopimazine (7.5 mg x 2 every 8 hours) or 16 mg/day of ondansetron (8 mg every 12 hours).

Metopimazine is primarily metabolized by a liver amidase in humans and therefore present a low risk on drug-drug interaction.

[27] Gastroparesis is a debilitating chronic gastrointestinal disorder characterized by delayed gastric emptying without evidence of mechanical obstruction.

Symptoms include nausea, vomiting, early satiety, postprandial fullness, bloating, and upper abdominal pain.

For the first step, 2-Methylthiophenothiazine [7643-08-5] (1) is protected by sequential reaction with sodium amide and acetic anhydride to give 1-[2-(Methylthio)-10H-phenothiazin-10-yl]ethanone [23503-69-7] (2).