Disease relevance of BIBP3226

• This decrease was blocked by BIBP3226, a Y(1) receptor antagonist, or by pertussis toxin, in agreement with Y(1) receptor activation [1].
• Although there was no major difference in the hemodynamic parameters among the groups, injection of [Leu(31),Pro(34)]-neuropeptide Y tended to further reduce cerebral perfusion during ischemia, while injection of BIBP3226 at 15 microg/kg appeared to have the opposite effect [2].
• The binding of tritium-labelled BIBP3226, N2-(diphenylacetyl)-N-[(4-hydroxy-phenyl)methyl]-D-arginine amide, to human neuroblastoma SK-N-MC cells was investigated [3].
• This effect of BIBP3226 on the gonadotrope axis occurred without apparent toxicity, but was accompanied by a transient decrease in body weight gain on the first day of treatment, suggesting an effect on appetite [4].
• BIBP3226 (N2-(diphenylacetyl)-N-[4-hydroxyphenyl)methyl]-D-arginine amide) has been used to examine the presence of neuropeptide Y Y1 receptors in 3 gastrointestinal epithelial preparations, namely the rat jejunum and descending colon mucosae and a human colonic adenocarcinoma cell line [5].

Psychiatry related information on BIBP3226

• The anxiogenic-like effect of BIBP3226 was not related to a decrease in general locomotor activity [6].
• BIBP3226 and 1229U91 (both 500 pmol) significantly decreased the time spent in active social interaction [7].

High impact information on BIBP3226

• QRFP-induced food intake was abolished by preadministration of BIBP3226, a specific antagonist for the Y1 neuropeptide Y receptor [8].
• Assays performed by using [125I][Leu31,Pro34]PYY in the presence of 1 microM BIBP3226 to block the Y1 receptor subtype revealed a pharmacological profile highly similar to the cloned Y5 receptor [9].
• These similarities together with the finding that BIBP3226, an anorexigenic Y1 receptor ligand, also binds to NPFF1 suggest a potential role for NPFF1 in feeding [10].
• Hindlimb vascular conductance was measured during infusion of BIBP3226 (Y(1)-receptor antagonist; 100 microg kg(-1)), prazosin (alpha(1)-receptor antagonist; 20 microg kg(-1)), and combined blockade [11].
• The effects of 100 nM NPY, but not PYY, were antagonized partially by the Y1 receptor selective antagonist BIBP3226 (0.1 micro M) [12].

Chemical compound and disease context of BIBP3226

• BIBP3226 or ethanol, when administered alone, did not alter motor activity or cortical event-related potentials (ERPs) but administration of BIBP3226 + EtOH reduced motor activity, reduced parietal cortical N1 ERP amplitude and increased frontal cortical N1 ERP latency [13].

Biological context of BIBP3226

• Additionally, [125I][Leu31,Pro34]PYY/BIBP3226-insensitive binding sites were not clearly detected in the vervet and human brains [14].
• BIBP3226, but not rauwolscine (a selective alpha2-adrenoceptor antagonist), abolished periarterial nerve stimulation-induced enhancement of angiotensin II-mediated renal vasoconstriction [15].
• BIBP3226, the selective Y1 antagonist, potently displaces [125I]NPY from its binding site IC50 = 1.91 x 10(-9) M [16].
• It is concluded that, at moderately high concentrations, the NPY Y1 receptor antagonist BIBP3226 and its entantiomer BIBP3435 are able to increase the [Ca2+ ]i in CHO cells either by stimulating another receptor or by directly affecting cellular mechanisms that are involved in calcium homeostasis [17].
• The selective Y1 receptor antagonist (1 microM BIBP3226) had no significant effect upon either peptide YY (PYY) responses or on electric field stimulated changes in electrogenic ion transport in rat jejunum mucosa [5].

Anatomical context of BIBP3226

• This stimulation was resistant to BIBP3226 a non-peptidergic antagonist at Y1 receptors, but it was significantly reduced in membranes treated with selective antibodies against the Gialpha subunits [18].
• Intracerebroventricular injection of a neuropeptide Y-Y1 receptor agonist increases while BIBP3226, a Y1 antagonist, reduces the infarct volume following transient middle cerebral artery occlusion in rats [2].
• NPY Y(1) antagonist BIBP3226 and mixed Y(1) antagonist/Y(4) agonist GR231118 are able to displace with low affinity, 50 -- 100 nM, the specific binding on NPFF receptors expressed in CHO cells as well as in rat dorsal spinal cord, an affinity however superior to those determined against Y(2), Y(4) or Y(5) receptors [19].
• Results from the present study showed that microinjection of the D1 receptor agonist SKF-38393 into the nucleus accumbens shell induced a suppression of NK activity that was reversed by BIBP3226 [20].
• Because cardiac myocytes express both Y1 and Y2 NPY receptors, we repeated the experiments in the presence of the receptor blockers, BIBP3226 and BIIE0246 [21].

Associations of BIBP3226 with other chemical compounds

• However, pretreatment with BIBO3304 or BIBP3226 significantly blocked the anti-immobility effects of NPY [22].
• Treatment with BIBP3226 was found to completely prevent NPY amplification of LHRH-induced LH surges in pentobarbital-blocked, proestrous rats, thus confirming a pituitary locus of action of the drug [23].
• Furthermore, BIBP3226 which is unable to inhibit the forskolin-stimulated cyclic AMP production mediated by NPFF(2) receptors, antagonizes the effect of NPFF, revealing the first antagonist of NPFF receptors [19].
• BIBP3226 {(R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)-methyl]-argininamide} was recently shown to display relatively high affinities for neuropeptide FF (NPFF) receptors and exhibit antagonist activities towards NPFF receptors in vitro [24].
• Effect of BIBP3226 on inositol phosphate accumulation and cytosolic calcium level in control and NPY Y1 receptor expressing CHO-K1 cells [25].

Gene context of BIBP3226

• BIBP3226, a nonpeptide Y1 receptor antagonist, as well as its opposite enantiomer, BIBP3435, which is inactive at Y1 receptors, blocked feeding elicited by NPY, [Leu31Pro34], or PYY at doses that did not cause overt behavioral dysfunction [26].
• 4. Y(1) receptor antagonists, BIBP3226 and BIBO3304 both increased basal I(sc) levels per se and inhibited subsequent PYY and Pro(34)PYY but not hPP or PYY(3 - 36) responses [27].
• NPY 2-36 was much less potent than NPY itself and pretreatment with BIBP3226 did not affect the inhibitory response [28].
• Pretreatment with the Y1 receptor-selective antagonist BIBP3226 (1 microM) failed to prevent the NPY-induced inhibition [29].
• BIBP3226 alone did not alter CRF release from hypothalamic explants [30].

Analytical, diagnostic and therapeutic context of BIBP3226

• Emulsion receptor autoradiography using a newly developed ligand, [(125)I]GR231118 in the presence of PYY, hPP or BIBP3226 (1 microM), pharmacologically established the Y(1) nature of these receptors [31].
• As one of the recently cloned Y5 receptors is synthesized in these regions, as shown by in-situ hybridization techniques, we suggest that the small population of [125I]PYY(3-36) binding sites which are sensitive to human PP and [Leu31,Pro34]NPY, but insensitive to BIBP3226, may represent binding to Y5 receptors [32].
• BIBP3226 potently blocked (pA2 = 7.36) the contractile effect of neuropeptide Y in the rabbit saphenous vein, a Y1 receptor bioassay and demonstrated nM affinity for Y1/[125I][Leu31,Pro34]peptide YY binding sites [33].
• When compared to the vehicle-treated control group, treatment with NPY or [Leu31,Pro34]-NPY (Y1 agonist) reduced viability of cultured SK-N-MC (Y1-expressing) human neuronal cells at 24 h after 1 h of OGD, while BIBP3226 (Y1 antagonist) improved viability [34].

References