Synonym
LY 215840; LY-215840; LY215840;
IUPAC/Chemical Name
Ergoline-8-carboxamide, N-(2-hydroxycyclopentyl)-6-methyl-1-(1-methylethyl)-, (8beta(1S,2R))-
InChi Key
IMSDOBUYDTVEHN-ILMFXRJHSA-N
InChi Code
InChI=1S/C24H33N3O2/c1-14(2)27-13-15-11-21-18(17-6-4-8-20(27)23(15)17)10-16(12-26(21)3)24(29)25-19-7-5-9-22(19)28/h4,6,8,13-14,16,18-19,21-22,28H,5,7,9-12H2,1-3H3,(H,25,29)/t16-,18-,19+,21-,22-/m1/s1
SMILES Code
[H][C@@]1(N(C)C[C@H](C(N[C@@H]2[C@H](O)CCC2)=O)C[C@@]13[H])CC4=CN(C(C)C)C5=C4C3=CC=C5
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
LY 215840 is a potent 5-hydroxytryptamine (5-HT)2 receptor antagonist.
In vitro activity:
To determine if the effects of paroxetine are mediated via modulation of the 5-HT system, this study treated macrophages with 5-HT or 5-HT receptor antagonist (LY215840) in the presence of LPS and/or paroxetine. 5-HT treatment by itself did not affect LPS-induced cytokine production. LY215840, however, reversed paroxetine's effect on LPS-induced TNFα production but not IL-6.
Reference: Int Immunopharmacol. 2015 Apr;25(2):485-92. https://pubmed.ncbi.nlm.nih.gov/25744603/
In vivo activity:
Serotonin (5-HT) stimulates aldosterone secretion from the rat adrenal gland through 5-HT(7) receptors. The aim of the present study was to investigate the transduction mechanisms associated with activation of 5-HT(7) receptors in rat glomerulosa cells. The stimulatory effect of 5-HT on aldosterone secretion and cAMP formation was significantly reduced by the 5-HT(7) receptor antagonist LY 215840.
Reference: Endocrinology. 2002 May;143(5):1748-60. https://pubmed.ncbi.nlm.nih.gov/11956157/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
395.55
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Durairaj H, Steury MD, Parameswaran N. Paroxetine differentially modulates LPS-induced TNFα and IL-6 production in mouse macrophages. Int Immunopharmacol. 2015 Apr;25(2):485-92. doi: 10.1016/j.intimp.2015.02.029. Epub 2015 Mar 2. PMID: 25744603; PMCID: PMC4373999.
2. Lenglet S, Louiset E, Delarue C, Vaudry H, Contesse V. Activation of 5-HT(7) receptor in rat glomerulosa cells is associated with an increase in adenylyl cyclase activity and calcium influx through T-type calcium channels. Endocrinology. 2002 May;143(5):1748-60. doi: 10.1210/endo.143.5.8817. PMID: 11956157.
3. Cushing DJ, Zgombick JM, Nelson DL, Cohen ML. LY215840, a high-affinity 5-HT7 receptor ligand, blocks serotonin-induced relaxation in canine coronary artery. J Pharmacol Exp Ther. 1996 Jun;277(3):1560-6. PMID: 8667223.
In vitro protocol:
1. Durairaj H, Steury MD, Parameswaran N. Paroxetine differentially modulates LPS-induced TNFα and IL-6 production in mouse macrophages. Int Immunopharmacol. 2015 Apr;25(2):485-92. doi: 10.1016/j.intimp.2015.02.029. Epub 2015 Mar 2. PMID: 25744603; PMCID: PMC4373999.
In vivo protocol:
1. Lenglet S, Louiset E, Delarue C, Vaudry H, Contesse V. Activation of 5-HT(7) receptor in rat glomerulosa cells is associated with an increase in adenylyl cyclase activity and calcium influx through T-type calcium channels. Endocrinology. 2002 May;143(5):1748-60. doi: 10.1210/endo.143.5.8817. PMID: 11956157.
2. Cushing DJ, Zgombick JM, Nelson DL, Cohen ML. LY215840, a high-affinity 5-HT7 receptor ligand, blocks serotonin-induced relaxation in canine coronary artery. J Pharmacol Exp Ther. 1996 Jun;277(3):1560-6. PMID: 8667223.
1: Durairaj H, Steury MD, Parameswaran N. Paroxetine differentially modulates LPS-induced TNFα and IL-6 production in mouse macrophages. Int Immunopharmacol. 2015 Apr;25(2):485-92. doi: 10.1016/j.intimp.2015.02.029. Epub 2015 Mar 2. PubMed PMID: 25744603; PubMed Central PMCID: PMC4373999.
2: Lenglet S, Louiset E, Delarue C, Vaudry H, Contesse V. Activation of 5-HT(7) receptor in rat glomerulosa cells is associated with an increase in adenylyl cyclase activity and calcium influx through T-type calcium channels. Endocrinology. 2002 May;143(5):1748-60. PubMed PMID: 11956157.
3: Meneses A, Terrón JA. Role of 5-HT(1A) and 5-HT(7) receptors in the facilitatory response induced by 8-OH-DPAT on learning consolidation. Behav Brain Res. 2001 Jun;121(1-2):21-8. PubMed PMID: 11275281.
4: Ishine T, Bouchelet I, Hamel E, Lee TJ. Serotonin 5-HT(7) receptors mediate relaxation of porcine pial veins. Am J Physiol Heart Circ Physiol. 2000 Mar;278(3):H907-12. PubMed PMID: 10710360.
5: Terrón JA. Antagonism of the relaxant 5-HT receptor in the dog basilar artery by the high-affinity 5-HT7 receptor ligand, LY215840. Proc West Pharmacol Soc. 1998;41:129-30. PubMed PMID: 9836268.
6: Brooks SA, Lachno DR, Obermeyer BD. Automated high-performance liquid chromatographic method for the analysis of two novel ergoline compounds in human plasma. J Chromatogr B Biomed Sci Appl. 1997 Apr 11;691(2):383-8. PubMed PMID: 9174275.
7: Cushing DJ, Zgombick JM, Nelson DL, Cohen ML. LY215840, a high-affinity 5-HT7 receptor ligand, blocks serotonin-induced relaxation in canine coronary artery. J Pharmacol Exp Ther. 1996 Jun;277(3):1560-6. PubMed PMID: 8667223.
8: Kauffman RF, Bean JS, Bloomquist WE, Cohen ML. Vascular serotonin 5-hydroxytryptamine2 receptor blockade by LY215840: lack of effect upon neointima formation in balloon-injured rat carotid arteries. J Pharmacol Exp Ther. 1993 Jul;266(1):450-5. PubMed PMID: 8331571.
9: Cohen ML, Robertson DW, Bloomquist WE, Wilson HC. LY215840, a potent 5-hydroxytryptamine (5-HT)2 receptor antagonist, blocks vascular and platelet 5-HT2 receptors and delays occlusion in a rabbit model of thrombosis. J Pharmacol Exp Ther. 1992 Apr;261(1):202-8. PubMed PMID: 1560366.
