N1-dansyl-spermine: a potent polyamine antagonist.
The potential polyamine antagonist action of N1-dansyl-spermine (a potent NMDA antagonist) was assessed in two in vivo mouse models of polyamine action. Co-administration of N1-dansyl-spermine (2-10 microg, i.c.v.) with spermine (100 microg, i.c.v.) resulted in a dose-dependent antagonism of the spermine-induced CNS excitation (body tremor and fatal tonic convulsions). In addition, the same dose of N1-dansyl-spermine antagonised spermine's enhancement of NMDA-induced convulsions. These results suggest that N1-dansyl-spermine is in vivo a potent antagonist of the CNS effects of spermine and of its action at the positive polyamine modulatory site on the NMDA receptor.
Kirby
Brian P
BP
Department of Pharmacology, School of Pharmacy, Trinity College, Dublin 2, Ireland. bkirby@rcsi.ie
Ryder
Sheila A
SA
Seiler
Nikolaus
N
Renault
Jacques
J
Shaw
Graham G
GG
D000818:Animals; D002490:Central Nervous System / Q000187:drug effects* / Q000503:physiopathology; D003619:Dansyl Compounds / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D007276:Injections, Intraventricular; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D011073:Polyamines / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D003619:Dansyl Compounds; D018690:Excitatory Amino Acid Agonists; C105932:N(1)-dansylspermine; D011073:Polyamines; D013096:Spermine; D016202:N-Methylaspartate