Activity of a new antiemetic agent: alizapride

Abstract

Alizapride is a methoxy-2-benzamide derivative three times more potent than its parent compound, metoclopramide, as an antagonist of apomorphine-induced emesis in dogs. The antiemetic activity of alizapride plus dexamethasone (DXM) was compared with that of placebo plus DXM in a randomized, double-blind, crossover study in cancer patients receiving cisplatin (DDP). Alizapride, given at the maximally tolerated dose of 4 mg/kg x 5, or placebo was given in a sequence determined by randomization during two successive, identical courses of antitumor chemotherapy. The antiemetic treatment was given 30 min before and 1.5, 3.5, 5.5, and 7.5 h after starting. DXM, in a dose of 12 mg, was given IV with the first administration of alizapride or placebo. A total of 39 patients completed the two courses of chemotherapy. The severity of gastrointestinal symptoms was influenced by previous treatment but not by the treatment sequence. Although our overall results suggest that alizapride does not add to the activity of DXM against DDP-induced amesis, a statistically significant difference favoring alizapride plus DXM was found among patients with the lowest gastrointestinal tolerance to DDP: women, patients under 50 years of age, and patients pretreated with chemotherapy including DDP and non-DDP agents. Side effects consisted of orthostatic hypotension, which was symptomatic in two patients, and a single occurrence of severe extrapyramidal syndrome. We conclude that alizapride is more active than placebo when combined with DXM for DDP-induced emesis in patients at high risk of severe nausea and vomiting. The severity of the side effects in this study indicates that a dose reduction of alizapride might be appropriate for further studies.

Development and validation of a stability-indicating HPLC-UV method for the determination of alizapride and its degradation products

“…1) is a substituted benzamide available as hydrochloride with potent anti-emetic properties. It is currently employed for the prevention of cancer chemotherapy and postoperative side-effects like nausea and vomiting and it is commercially available as injectable solution and tablets [1,2]. Several HPLC methods have been reported in literature for AL analysis but they are mainly related to its determination in biological fluids [3][4][5][6][7].…”

Options for the Prevention and Management of Acute Chemotherapy-Induced Nausea and Vomiting in Children

“…[76] Domperidone was given 30 minutes prior to the first morphine-induced emesis in dogs. [80] More recent human studies suggest that alizapride is, in fact, inferior to metoclopramide when Pediatric oncologists commonly prescribed phenothiazines in given as monotherapy, or in combination with a corticosteroid or the 1980s, despite a paucity of controlled clinical trials, since little benzodiazepine. [61,81] However, alizapride does appear to be less else was available.…”

Design, Synthesis, Molecular Docking, and In Vitro Antibacterial Evaluation of Benzotriazole-Based β-Amino Alcohols and Their Corresponding 1,3-Oxazolidines

“…Azoles, particularly the benzotriazole nucleus has a key role in both heterocyclic chemistry and medicinal chemistry. − Examples include the extensive use of benzotriazole-based compounds in the treatment of a wide range of diseases, including as anticarcinogenic, , antibacterial and antifungal, − and antimicrobial, antiprotozoal, antiviral, antimycobacterial, and antitubulin agents . Furthermore, it should be noted that benzotriazole scaffolds have stacking interactions because of the conjugated benzene ring structure, which forms hydrogen bonds with a number of enzymes and receptors .…”