Disease relevance of (2R)-2-[(2,2-diphenylacetyl)amino]-5-guanidino-N-[[4-(ureidomethyl)phenyl]methyl]pentanamide

• In addition, hyperphagia was partially reversed by intracerebroventricular administration of the NPY Y1 receptor antagonist BIBO3304 [1].

Psychiatry related information on (2R)-2-[(2,2-diphenylacetyl)amino]-5-guanidino-N-[[4-(ureidomethyl)phenyl]methyl]pentanamide

• We used a NPY-Y1 receptor specific antagonist, BIBO3304, to examine whether NPY is involved in orexin-induced feeding behavior [2].

High impact information on (2R)-2-[(2,2-diphenylacetyl)amino]-5-guanidino-N-[[4-(ureidomethyl)phenyl]methyl]pentanamide

• NPY increased cell-surface localization of HAY1S352* receptors, whereas the distribution of both mutants was unaltered by BIBO3304 [3].
• Intracerebroventricular injections (0.03 nmole-3 nmole) of NPY, [Leu(31)Pro(34)]PYY (Y(1) agonist), NPY(13-36) (Y(2) agonist), BIBP3226, BIBO3304 (Y(1) antagonists) and BIIE0246 (Y(2) antagonist) were performed 30 min prior to testing in the mouse forced swimming test and open field [4].
• The effect of both ghrelin and GHRP-6 on food intake was blocked by preadministration of a Y1 NPY receptor antagonist (BIBO3304) [5].
• 3. The Y1 receptor antagonist BIBO3304 blocked responses to the Y1 agonist at the lower doses, but only partially inhibited at the higher doses tested in Y2+/+ [6].
• 4 BIBO3304 and BIIE0246 elevated mucosal ion transport, indicating blockade of inhibitory mucosal tone in Y(2)+/+ tissue [7].

Biological context of (2R)-2-[(2,2-diphenylacetyl)amino]-5-guanidino-N-[[4-(ureidomethyl)phenyl]methyl]pentanamide

• Interestingly, high percentage of [(125)I]-GR231118/BIBO3304-insensitive binding sites were detected in few areas [8].
• On the other hand, using hippocampal membrane preparations, displacement curves with Hill coefficients close to unity were only obtained in the presence of Mn2+ ions, yielding a binding profile of receptors with low affinity for [Leu31,Pro34]NPY (IC50 = 50 nM) and for BIBO3304 (IC50 > 10,000 nM) [9].

Anatomical context of (2R)-2-[(2,2-diphenylacetyl)amino]-5-guanidino-N-[[4-(ureidomethyl)phenyl]methyl]pentanamide

• BIBO3304 abolished residual Y(1)-mediated NPY responses in Y(2)-/- smooth muscle [7].
• A Y1 receptor antagonist (BIBO3304) was infused (25 microg/h) into the third cerebral ventricle (III-V) from 2 h before EB injection for 24 h, and had no effect on the ensuing LH surge [10].
• In order to further classify receptor subtypes in the brain, we performed receptor binding studies using rat cortical and hippocampal membranes and, in particular, studied the effects of different ion compositions of the buffer on the binding behaviour of several NPY agonists and the Y1 receptor antagonist BIBO3304 [9].
• Finally, the selective antagonistic properties of BIBO3304 were demonstrated in a Y1 bioassay (rabbit saphenous vein; pA2 value of 9.04) while being inactive in Y2 (rat vas deferens) and Y4 (rat colon) bioassays [11].

Gene context of (2R)-2-[(2,2-diphenylacetyl)amino]-5-guanidino-N-[[4-(ureidomethyl)phenyl]methyl]pentanamide

• The Y(1) antagonists, BIBP3226 and BIBO3304 virtually abolished Pro(34)PYY and PYY responses while PYY(3-36) responses were selectively inhibited by the Y(2) antagonist, BIIE0246 [12].

References