Binding profile of benextramine at neuropeptide Y receptor subtypes in rat brain areas.
Binding studies in rat whole brain, frontoparietal cortex and brainstem membrane preparations revealed that benextramine displaced [3H]neuropeptide Y specific binding from a low and a high affinity site with IC50 values in the microM (36 +/- 2, 4.4 +/- 1.4 and 300 +/- 120 microM, respectively) and the pM (29.3 +/- 12.1, 0.35 +/- 0.11 and 0.42 +/- 0.03 pM, respectively) range, whereas in rat hippocampus benextramine displaced [3H]neuropeptide Y specific binding from one site only with an IC50 value of 22.8 +/- 5.7 microM. With the exception of frontoparietal cortex binding assay, benextramine was not able to completely inhibit [3H]neuropeptide Y specific binding revealing the presence of a benextramine nonsensitive third binding site. Benextramine pretreatment followed by membrane washing demonstrated that benextramine inhibited irreversibly both high and low affinity sites.
Melchiorre
C
C
Department of Pharmaceutical Sciences, University of Bologna, Italy.
Romualdi
P
P
Bolognesi
M L
ML
Donatini
A
A
Ferri
S
S
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D003198:Computer Simulation; D003538:Cystamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D003959:Diamines / Q000378:metabolism / Q000494:pharmacology; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010296:Parietal Lobe / Q000187:drug effects / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000187:drug effects / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D003959:Diamines; D017476:Receptors, Neuropeptide Y; C092427:CM 178-78; C029998:benextramine; D003538:Cystamine