The antiemetic profile of zacopride.
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.
Smith
W L
WL
Department of Pharmacology, A. H. Robins Company, Inc., Richmond, VA 23261-6609.
Alphin
R S
RS
Jackson
C B
CB
Sancilio
L F
LF
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors; D001058:Apomorphine / Q000037:antagonists & inhibitors; D001549:Benzamides / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D003300:Copper / Q000037:antagonists & inhibitors; D019327:Copper Sulfate; D004285:Dogs; D005260:Female; D006633:Histamine Antagonists; D008297:Male; D019894:Peptide YY; D010455:Peptides / Q000037:antagonists & inhibitors; D010862:Pilocarpine / Q000037:antagonists & inhibitors; D011526:Protoveratrines / Q000037:antagonists & inhibitors; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control
D000932:Antiemetics; D000970:Antineoplastic Agents; D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D006633:Histamine Antagonists; D010455:Peptides; D011526:Protoveratrines; D010862:Pilocarpine; D019894:Peptide YY; D003300:Copper; C055971:zacopride; D019327:Copper Sulfate; D001058:Apomorphine