Inhibition of cisplatin-induced emesis in ferrets by the non-NMDA receptor antagonists NBQX and CNQX.
The excitatory amino acid (EAA) receptor antagonists, 2,3-dihydroxy-6-nitro-7-sulphamoylbenzo(f)quinoxaline (NBQX) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), which preferentially block non-N-methyl-D-aspartate (non-NMDA) subtypes of EAA receptors, effectively inhibit cisplatin-induced emesis in ferrets. A high dose of cisplatin (10 mg/kg i.v.) was used which induced emesis in all saline-treated control ferrets. At 10 mg/kg i.v., NBQX totally prevented cisplatin-induced emesis in 5 of 6 ferrets and CNQX totally prevented emesis in 3 of 5 ferrets. By comparison, each of the 5-HT3 inhibitors, zacopride and ondansetron, at 1.0 mg/kg i.v. (a dose considered in the high therapeutic range for controlling emesis by these compounds), totally prevented emesis in 2 of 5 ferrets. It is concluded that non-NMDA antagonists effectively inhibit cisplatin-induced emesis. They are potential antiemetic compounds, alone or in combination with 5-HT3 antagonists or other more conventional drugs of choice.
CNS Division, Novo Nordisk A/S, Måløv, Denmark.
A
A
Fink-Jensen
M E
ME
Judge
J B
JB
Hansen
P
P
Jacobsen
L
L
Turski
J
J
Olney
T
T
Honoré
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002945:Cisplatin / Q000037:antagonists & inhibitors*; D005106:Exploratory Behavior / Q000187:drug effects; D005289:Ferrets; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D017294:Ondansetron; D011810:Quinoxalines / Q000494:pharmacology*; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors; D012702:Serotonin Antagonists / Q000494:pharmacology; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007093:Imidazoles; D011810:Quinoxalines; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D012702:Serotonin Antagonists; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D017294:Ondansetron; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C055971:zacopride; D002945:Cisplatin