1,5-(Diethylamino)piperidine, a novel spermidine analogue that more specifically activates the N-methyl-D-aspartate receptor-associated polyamine site.
We have investigated the action of 1,5-(diethylamino)piperidine (DEAP), a novel spermidine analogue that activates the polyamine site associated with the N-methyl-D-aspartate receptor. DEAP increased [3H]dizocilpine ([3H]MK801) binding to rat brain membranes with a potency similar to that of spermine and spermidine, but with a somewhat greater efficacy. Unlike other polyamines, however, DEAP did not exhibit low affinity inhibition of [3H] dizocilpine binding, suggesting that it binds more selectively to the polyamine site. DEAP increased the equilibrium affinity of [3H]dizocilpine. The increase in affinity was due to slowed dissociation, as well as a small increase in the association rate of [3H]dizocilpine. All of these effects of DEAP could be reversed by arcaine. These data illustrate the utility of DEAP as a novel polyamine agonist at the N-methyl-D-aspartate receptor complex. However, these data fail to support the hypothesis that polyamines activate the N-methyl-D-aspartate receptor by a mechanism similar to that of glutamate and glycine.
Reynolds
I J
IJ
Department of Pharmacology, University of Pittsburgh, Pennsylvania 15261.
D000494:Allosteric Regulation; D000818:Animals; D001665:Binding Sites; D016291:Dizocilpine Maleate / Q000378:metabolism; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D011073:Polyamines / Q000494:pharmacology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D013095:Spermidine / Q000031:analogs & derivatives*; D014316:Tritium
D010880:Piperidines; D011073:Polyamines; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; C075308:1,5-(diethylamino)piperidine; D016291:Dizocilpine Maleate; D008274:Magnesium; D013095:Spermidine