PT  - JOURNAL ARTICLE
AU  - Doods, H N
AU  - Wienen, W
AU  - Entzeroth, M
AU  - Rudolf, K
AU  - Eberlein, W
AU  - Engel, W
AU  - Wieland, H A
TI  - Pharmacological characterization of the selective nonpeptide neuropeptide Y Y1 receptor antagonist BIBP 3226.
DP  - 1995 Oct 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 136--142
VI  - 275
IP  - 1
4099  - http://jpet.aspetjournals.org/content/275/1/136.short
4100  - http://jpet.aspetjournals.org/content/275/1/136.full
SO  - J Pharmacol Exp Ther1995 Oct 01; 275
AB  - The present study was undertaken to investigate the in vitro and in vivo pharmacological profile of the novel, nonpeptide neuropeptide Y (NPY) Y1-selective antagonist, BIBP 3226 [(R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-D-arginine-am ide], and a recently described peptidic structure [Ile-Glu-Pro-Orn-Tyr-Arg-Leu-Arg-Tyr-NH2, cyclic (2,4&#039;), (2&#039;,4)-diamide]. BIBP 3226 antagonized the NPY Y1 receptor-mediated decrease in the twitch response in the rabbit vas deferens preparation with a pKb value of 6.98 +/- 0.06 (n = 16). It showed no affinity (EC50 &amp;gt; 1 microM) for NPY Y2 receptors in the rat vas deferens. NPY-induced increases in perfusion pressure in the isolated perfused rat kidney and rabbit ear preparations were antagonized with IC50 values of 26.8 +/- 4.5 (n = 4) and 214 +/- 30 nM (n = 4), respectively. The NPY-mediated potentiation of the noradrenaline elicited increase in perfusion pressure in the rat mesenteric bed was antagonized with an IC50 value of 976 (542-1760) nM. The NPY-induced increase in blood pressure in the pithed rat was inhibited by BIBP 3226 dose-dependently (ED50 = 0.11 +/- 0.03 mg/kg i.v.), whereas no effect of BIBP 3226 (1 mg/kg i.v.) was observed for the noradrenaline-, angiotensin-, endothelin- or vasopressin-induced pressor response. The data presented demonstrate that BIBP 3226 is a competitive and NPY Y1-selective antagonist. The peptidic compound proved to possess high potency for NPY Y1 receptors, but showed both agonistic as well as antagonistic properties.(ABSTRACT TRUNCATED AT 250 WORDS)