BIIE-0246

BIIE-0246
Clinical data
Other names	BIIE-0246
Identifiers
	IUPAC name N-[(1S)-4-[(Aminoiminomethyl)amino]-1-[([2-(3,5-dioxo-1,2-diphenyl-1,2,4-triazolidin-4-yl)ethyl]amino)carbonyl]butyl]-1-(2-[4-(6,11-dihydro-6-oxo-5H-dibenz[b,e]azepin-11-yl)-1-piperazinyl]-2-oxoethyl)cyclopentaneacetamide;
CAS Number	246146-55-4 ;
PubChem CID	9811493;
IUPHAR/BPS	1547;
ChemSpider	7987248 ;
UNII	N3Z657H81X;
CompTox Dashboard (EPA)	DTXSID40179360 ;
Chemical and physical data
Formula	C49H57N11O6
Molar mass	896.066 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C3N(c1ccccc1)N(c2ccccc2)C(=O)N3CCNC(=O)[C@@H](NC(=O)CC4(CCCC4)CC(=O)N8CCN(C7c5c(cccc5)NC(=O)c6ccccc67)CC8)CCC/N=C(\N)N;
	InChI InChI=1S/C49H57N11O6/c50-46(51)53-25-13-22-40(45(64)52-26-27-58-47(65)59(34-14-3-1-4-15-34)60(48(58)66)35-16-5-2-6-17-35)54-41(61)32-49(23-11-12-24-49)33-42(62)56-28-30-57(31-29-56)43-36-18-7-8-19-37(36)44(63)55-39-21-10-9-20-38(39)43/h1-10,14-21,40,43H,11-13,22-33H2,(H,52,64)(H,54,61)(H,55,63)(H4,50,51,53)/t40-,43?/m0/s1 ; Key:RSJAXPUYVJKAAA-JPGJPTAESA-N ;
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BIIE-0246 is a drug used in scientific research which acts as a potent and selective antagonist for the Neuropeptide Y receptor Y₂.^[1] It was one of the first non-peptide Y₂-selective antagonists developed, and remains among the most widely used tools for studying this receptor. It has been used to demonstrate a role for the Y₂ subtype as a presynaptic autoreceptor limiting further neuropeptide Y release,^[2]^[3] as well as modulating dopamine^[4] and acetylcholine release.^[5] It has also been shown to produce several behavioural effects in animals, including reducing alcohol consumption in addicted rats^[6]^[7] and anxiolytic effects,^[8] although while selective Y₂ agonists are expected to be useful as anorectics,^[9]^[10] BIIE-0246 did not appear to increase appetite when administered alone.^[11]

References

^ Doods H, Gaida W, Wieland HA, Dollinger H, Schnorrenberg G, Esser F, Engel W, Eberlein W, Rudolf K (November 1999). "BIIE0246: a selective and high affinity neuropeptide Y Y(2) receptor antagonist". European Journal of Pharmacology. 384 (2–3): R3–5. doi:10.1016/S0014-2999(99)00650-0. PMID 10611450.
^ King PJ, Williams G, Doods H, Widdowson PS (May 2000). "Effect of a selective neuropeptide Y Y(2) receptor antagonist, BIIE0246 on neuropeptide Y release". European Journal of Pharmacology. 396 (1): R1–3. doi:10.1016/S0014-2999(00)00230-2. PMID 10822055.
^ Malmström RE, Lundberg JO, Weitzberg E (March 2002). "Autoinhibitory function of the sympathetic prejunctional neuropeptide Y Y(2) receptor evidenced by BIIE0246". European Journal of Pharmacology. 439 (1–3): 113–9. doi:10.1016/S0014-2999(02)01371-7. PMID 11937100.
^ Adewale AS, Macarthur H, Westfall TC (May 2007). "Neuropeptide Y-induced enhancement of the evoked release of newly synthesized dopamine in rat striatum: mediation by Y2 receptors". Neuropharmacology. 52 (6): 1396–402. doi:10.1016/j.neuropharm.2007.01.018. PMID 17382974.
^ Herring N, Lokale MN, Danson EJ, Heaton DA, Paterson DJ (March 2008). "Neuropeptide Y reduces acetylcholine release and vagal bradycardia via a Y2 receptor-mediated, protein kinase C-dependent pathway". Journal of Molecular and Cellular Cardiology. 44 (3): 477–85. doi:10.1016/j.yjmcc.2007.10.001. PMID 17996892.
^ Thorsell A, Rimondini R, Heilig M (October 2002). "Blockade of central neuropeptide Y (NPY) Y2 receptors reduces ethanol self-administration in rats". Neuroscience Letters. 332 (1): 1–4. doi:10.1016/S0304-3940(02)00904-7. PMID 12377370.
^ Rimondini R, Thorsell A, Heilig M (February 2005). "Suppression of ethanol self-administration by the neuropeptide Y (NPY) Y2 receptor antagonist BIIE0246: evidence for sensitization in rats with a history of dependence". Neuroscience Letters. 375 (2): 129–33. doi:10.1016/j.neulet.2004.10.084. PMID 15670655.
^ Bacchi F, Mathé AA, Jiménez P, Stasi L, Arban R, Gerrard P, Caberlotto L (December 2006). "Anxiolytic-like effect of the selective neuropeptide Y Y2 receptor antagonist BIIE0246 in the elevated plus-maze". Peptides. 27 (12): 3202–7. doi:10.1016/j.peptides.2006.07.020. PMID 16959374.
^ Félétou M, Levens NR (October 2005). "Neuropeptide Y2 receptors as drug targets for the central regulation of body weight". Current Opinion in Investigational Drugs. 6 (10): 1002–11. PMID 16259221.
^ Parker SL, Balasubramaniam A (February 2008). "Neuropeptide Y Y2 receptor in health and disease". British Journal of Pharmacology. 153 (3): 420–31. doi:10.1038/sj.bjp.0707445. PMC 2241788. PMID 17828288.
^ Scott V, Kimura N, Stark JA, Luckman SM (July 2005). "Intravenous peptide YY3-36 and Y2 receptor antagonism in the rat: effects on feeding behaviour". Journal of Neuroendocrinology. 17 (7): 452–7. doi:10.1111/j.1365-2826.2005.01330.x. PMID 15946163.

[pmid10611450-1] Doods H, Gaida W, Wieland HA, Dollinger H, Schnorrenberg G, Esser F, Engel W, Eberlein W, Rudolf K (November 1999). "BIIE0246: a selective and high affinity neuropeptide Y Y(2) receptor antagonist". European Journal of Pharmacology. 384 (2–3): R3–5. doi:10.1016/S0014-2999(99)00650-0. PMID 10611450.

[pmid10822055-2] King PJ, Williams G, Doods H, Widdowson PS (May 2000). "Effect of a selective neuropeptide Y Y(2) receptor antagonist, BIIE0246 on neuropeptide Y release". European Journal of Pharmacology. 396 (1): R1–3. doi:10.1016/S0014-2999(00)00230-2. PMID 10822055.

[pmid11937100-3] Malmström RE, Lundberg JO, Weitzberg E (March 2002). "Autoinhibitory function of the sympathetic prejunctional neuropeptide Y Y(2) receptor evidenced by BIIE0246". European Journal of Pharmacology. 439 (1–3): 113–9. doi:10.1016/S0014-2999(02)01371-7. PMID 11937100.

[pmid17382974-4] Adewale AS, Macarthur H, Westfall TC (May 2007). "Neuropeptide Y-induced enhancement of the evoked release of newly synthesized dopamine in rat striatum: mediation by Y2 receptors". Neuropharmacology. 52 (6): 1396–402. doi:10.1016/j.neuropharm.2007.01.018. PMID 17382974.

[pmid17996892-5] Herring N, Lokale MN, Danson EJ, Heaton DA, Paterson DJ (March 2008). "Neuropeptide Y reduces acetylcholine release and vagal bradycardia via a Y2 receptor-mediated, protein kinase C-dependent pathway". Journal of Molecular and Cellular Cardiology. 44 (3): 477–85. doi:10.1016/j.yjmcc.2007.10.001. PMID 17996892.

[pmid12377370-6] Thorsell A, Rimondini R, Heilig M (October 2002). "Blockade of central neuropeptide Y (NPY) Y2 receptors reduces ethanol self-administration in rats". Neuroscience Letters. 332 (1): 1–4. doi:10.1016/S0304-3940(02)00904-7. PMID 12377370.

[pmid15670655-7] Rimondini R, Thorsell A, Heilig M (February 2005). "Suppression of ethanol self-administration by the neuropeptide Y (NPY) Y2 receptor antagonist BIIE0246: evidence for sensitization in rats with a history of dependence". Neuroscience Letters. 375 (2): 129–33. doi:10.1016/j.neulet.2004.10.084. PMID 15670655.

[pmid16959374-8] Bacchi F, Mathé AA, Jiménez P, Stasi L, Arban R, Gerrard P, Caberlotto L (December 2006). "Anxiolytic-like effect of the selective neuropeptide Y Y2 receptor antagonist BIIE0246 in the elevated plus-maze". Peptides. 27 (12): 3202–7. doi:10.1016/j.peptides.2006.07.020. PMID 16959374.

[pmid16259221-9] Félétou M, Levens NR (October 2005). "Neuropeptide Y2 receptors as drug targets for the central regulation of body weight". Current Opinion in Investigational Drugs. 6 (10): 1002–11. PMID 16259221.

[pmid17828288-10] Parker SL, Balasubramaniam A (February 2008). "Neuropeptide Y Y2 receptor in health and disease". British Journal of Pharmacology. 153 (3): 420–31. doi:10.1038/sj.bjp.0707445. PMC 2241788. PMID 17828288.

[pmid15946163-11] Scott V, Kimura N, Stark JA, Luckman SM (July 2005). "Intravenous peptide YY3-36 and Y2 receptor antagonism in the rat: effects on feeding behaviour". Journal of Neuroendocrinology. 17 (7): 452–7. doi:10.1111/j.1365-2826.2005.01330.x. PMID 15946163.

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