The Antiemetic Profile of Zacopride

Abstract

The antiemetic activity of zacopride against a variety of emetogenic agents has been determined in dogs. Zacopride was highly effective in inhibiting emesis due to a wide range of cancer chemotherapeutic agents, particularly cisplatin. It was well absorbed orally since the dose of zacopride required to inhibit cisplatin-induced emesis in dogs by 90% was 28 micrograms kg-1 both by i.v. and p.o. routes. Further, zacopride (1 mg kg-1 p.o.), administered after the onset of cisplatin-induced emesis, reduced the number of subsequent emetic episodes by 91%. Zacopride at 0.1, 1, or 3.16 mg kg-1 p.o. or i.v., reduced the number of emetic episodes due to dacarbazine, mechlorethamine, adriamycin, actinomycin D, or peptide YY by 100, 100, 86, 96 and 79%, respectively. However, zacopride was not effective in inhibiting emesis due to either apomorphine, copper sulphate, protoveratrine A, histamine, or pilocarpine. No adverse effects attributed to zacopride were observed. Zacopride is thus a unique and potent antiemetic agent as it selectively inhibits the emetic response to cancer chemotherapy agents and peptide YY.

The Effects of Orally Administered Y-25130, a Selective Serotonin3-Receptor Antagonist, on Chemotherapeutic Agent-Induced Emesis

“…Most studies on the antiemetic activities of 5-HT3 receptor antagonists have been conducted with only a 3 to 5 hr observation period (11,15,19). To evaluate the antiemetic activity of the test drugs during a longer period, we have observed the vomiting for 24 hr after the treatment of dogs with cisplatin and ferrets with dox orubicin/cyclophosphamide.…”

“…The procedure used was a modification of the method described by Smith et al (15). Dogs were starved for 22 hr and then fed for a 2-hr period before treatment with cisplatin (3 mg/kg, i.v.).…”

Signals for nausea and emesis: Implications for models of upper gastrointestinal diseases

“…Cat Cytotoxic drugs: Cisplatin , Cyclophosphamide (Fetting et al, 1982) Intragastric irritants: Copper sulfate (Kayashima and Hyama, 1976) Motion (Crampton and Daunton, 1983) Apomorphine (Costello and Borison, 1977) Morphine (Villablanca et al, 1984) Radiation (Rabin et al, 1986b) (Rabin et al, 1986b) Nicotine (Beleslin et al, 1981) Hormones and neurotransmitters: Angiotensin II (Rabin et al, 1986a) Other: Amphetamine (Rabin and Hunt, 1992) Dog Cytotoxic drugs: Cisplatin (Gylys et al, 1979), Cyclophosphamide (Amber et al, 1990) Intragastric irritants: Ipecac (Gardner et al, 1996), Copper sulfate (Kayashima and Hayama, 1975) LiCl (Vavilova and Kassil, 1984) Apomorphine (Harrison et al, 1972) Morphine (Lefebvre et al, 1981) Radiation (Cooper and Mattsson, 1979) Nicotine (Vig, 1990) Hormones and neurotransmitters: CCK (Levine et al, 1984), Vasopressin (Wu et al, 1985), Peptide YY (Smith et al, 1989) Ferret Cytotoxic drugs: Cisplatin, cyclophosphamide (Andrews et al, 1990) Intragastric irritants: Copper sulfate, ipecac, NaCl, KCl (Andrews et al, 1990) LiCl (Rabin and Hunt, 1992) Apomorphine (Andrews et al, 1990) Morphine (Barnes et al, 1991) Radiation (Andrews et al, 1990) Guinea pig Intragastric irritants: LiCl (Braveman, 1974) …”

Nitrogen-containing heteroalicycles with serotonin receptor binding affinity: Development of gastroprokinetic and antiemetic agents

“…11). 98 Moreover, 5-HT 3 receptor antagonists may represent important drugs as recent data have suggested the existence of 5-HT 3 receptor binding sites in the brain, 11 and several of the 5-HT 3 receptor antagonists are currently being evaluated in clinics as antischizophrenic, antimigrainic, and anxiolytic agents 99 -102 and as drugs for gastrointestinal dysfunctions such as irritable bowel syndrome. 103, 104 We have developed mosapride, which showed a potent gastroprokinetic activity without dopamine D 2 receptor antagonistic activity.…”