LY334370
(Synonyms: 4-氟-N-(3-(1-甲基哌啶-4-基)-1H-吲哚-5-基)苯甲酰胺盐酸盐) 目录号 : GC36511
A 5-HT1F receptor agonist
Cas No.:182563-08-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
LY334370 is an agonist of the serotonin (5-HT) receptor subtype 5-HT1F (Kd = 0.446 nM).1 It is selective for 5-HT1F over other G protein-coupled 5-HT receptor subtypes with Ki values ranging from 16.4 to greater than 3,000 nM in radioligand binding assays. LY334370 inhibits forskolin-induced cAMP accumulation in mouse L-M(TK-) cell membranes expressing the recombinant human 5-HT1F receptor (EC50 = 1.51 nM).2 It decreases electrically stimulated extravasation of plasma proteins in the dura mater in a guinea pig trigeminal nerve model of migraine headache.
1.Wainscott, D.B., Krushinski, J.H., Jr., Audia, J.E., et al.[3H]LY334370, a novel radioligand for the 5-HT1F receptor. I. In vitro characterization of binding propertiesNaunyn Schmiedebergs Arch. Pharmacol.371(3)169-177(2005) 2.Johnson, K.W., Schaus, J.M., Durkin, M.M., et al.5-HT1F receptor agonists inhibit neurogenic dural inflammation in guinea pigsNeuroreport8(9-10)2237-2240(1997)
| Cas No. | 182563-08-2 | SDF | |
| 别名 | 4-氟-N-(3-(1-甲基哌啶-4-基)-1H-吲哚-5-基)苯甲酰胺盐酸盐 | ||
| Canonical SMILES | O=C(C1=CC=C(F)C=C1)NC2=CC3=C(C=C2)NC=C3C4CCN(C)CC4 | ||
| 分子式 | C21H22FN3O | 分子量 | 351.42 |
| 溶解度 | DMSO: ≥ 55.5 mg/mL (157.93 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.8456 mL | 14.228 mL | 28.456 mL |
| 5 mM | 0.5691 mL | 2.8456 mL | 5.6912 mL |
| 10 mM | 0.2846 mL | 1.4228 mL | 2.8456 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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[3H]LY334370, a novel radioligand for the 5-HT1F receptor. I. In vitro characterization of binding properties
Naunyn Schmiedebergs Arch Pharmacol 2005 Mar;371(3):169-77.PMID:15900510DOI:10.1007/s00210-005-1035-9.
[(3)H]LY334370 was developed as a radioligand to study the characteristics of this compound's interaction with the 5-HT(1F) receptor. Monovalent or divalent cations did not enhance the binding of [(3)H]LY334370 to the cloned human 5-HT(1F) receptor. In the presence of MgCl(2), the time to reach equilibrium was approximately 2 h, while in its absence equilibrium was reached in less than 1 h. [(3)H]LY334370 had high affinity for the cloned human 5-HT(1F) receptor (K(d)=0.446 nM) and the 5-HT(1F) receptor in rat brain (K(d)=0.388 nM). The expression density of 5-HT(1F) receptors, as determined by binding to homogenates of cortical regions from rat, was low (B(max)=79.1 fmol/mg protein). There was a statistically significant correlation between the apparent pK(i) for inhibition of [(3)H]LY334370 binding and the pEC(50) for stimulation of [(35)S]GTPgammaS binding to homogenates of cells expressing the cloned human 5-HT(1F) receptor. In addition, there was a statistically significant correlation between the apparent pK(i) for inhibition of [(3)H]LY334370 binding to the cloned human 5-HT(1F) receptor and the pID(50) for inhibition of trigeminal nerve stimulated dural plasma protein extravasation in the guinea pig. The conclusion from these studies is that [(3)H]LY334370 is a high affinity radioligand which can be used for the study of the 5-HT(1F) receptor in rat brain or in cells transformed with the human 5-HT(1F) receptor.
[3H]LY334370, a novel radioligand for the 5-HT1F receptor. II. Autoradiographic localization in rat, guinea pig, monkey and human brain
Naunyn Schmiedebergs Arch Pharmacol 2005 Mar;371(3):178-84.PMID:15900511DOI:10.1007/s00210-005-1036-8.
LY334370 is a high affinity, selective agonist at the 5-HT(1F) receptor. On this basis, the tritiated compound was examined for its utility in autoradiography to localize the 5-HT(1F) receptor in rat and guinea pig brain regions. Specific 5-HT(1F) receptor binding in rat brain was found in layers 4-5 of all cortical regions examined, as well as olfactory bulb and tubercle, nucleus accumbens, caudate putamen, parafascicular nucleus of the thalamus, medial mammillary nucleus, the CA3 region of the hippocampus, subiculum, and several amygdaloid nuclei. In guinea pig brain, the [(3)H]LY334370 binding sites were found at highest density in claustrum, but also in a layer of the cortex, caudate putamen, nucleus accumbens, thalamus, and medial mammillary nucleus. Some species differences in the distribution of the 5-HT(1F) receptor were noted. Side by side comparison of rat brain autoradiography with [(3)H]LY334370 and [(3)H]sumatriptan showed labeling in the same brain regions. Preliminary binding studies in rhesus monkey and human brain sections showed [(3)H]LY334370 binding in cortical layers 4-5, subiculum (in the monkey), and the granule cell layer of the cerebellum. These findings suggest a discrete localization of the 5-HT(1F) receptor in the rat, guinea pig, monkey and human brain, and confirms the utility of [(3)H]LY334370 as a potential tool to explore further the localization and possible functions of the 5-HT(1F) receptor.
Crystal forms of LY334370 HCl: isolation, solid-state characterization, and physicochemical properties
J Pharm Sci 2003 Jun;92(6):1196-205.PMID:12761809DOI:10.1002/jps.10373.
LY334370 HCl, a 5HT1f agonist investigated for the treatment of migraines, was identified in five crystal forms: three anhydrates (I-III), a dihydrate, and an acetic acid solvate. The identification and characterization of these crystal forms by optical microscopy, differential scanning calorimetry, thermogravimetric and moisture sorption analyses, solid-state NMR spectroscopy, and X-ray crystallography (Form I only) are presented. Physical properties, including hygroscopicity, solubility, and intrinsic dissolution rate, were assessed for Form I and the dihydrate, the two most viable crystal forms for commercial development. Surprisingly, anhydrous Form I was found to be the thermodynamically most stable crystal form in water, dissolving six times slower than the dihydrate, a difference that correlates well with the rank order of aqueous solubility.
Selective seratonin 1F (5-HT(1F)) receptor agonist LY334370 for acute migraine: a randomised controlled trial
Lancet 2001 Oct 13;358(9289):1230-4.PMID:11675061DOI:10.1016/s0140-6736(01)06347-4.
Background: Triptans (5-HT(1B/1D) receptor agonists) are effective drugs for acute migraine, but the side-effect of coronary vasoconstriction restricts their use in patients who are at risk of coronary artery disease. We have studied the efficacy of LY334370, a selective serotonin 1F (5-HT(1F)) receptor agonist with preclinical efficacy and no vasoconstriction, for migraine relief. Methods: We gave LY334370 (20, 60, or 200 mg) or placebo to 99 outpatients with moderate or severe migraine headaches in a double blind, parallel group study. We measured efficacy by sustained response, response at 2 h, pain free at 2 h, and sustained pain free. Findings: The proportions of patients with defined endpoints for placebo and LY334370 20, 60, and 200 mg, respectively, were: sustained response, two of 26 (8%), three of 22 (14%), 11 of 30 (37%), and 11 of 21 (52%) (dose response p<0.001); response, five of 26 (19%), four of 22 (18%), 15 of 30 (50%), and 15 of 21 (71%) (p<0.001); pain free, one of 26 (4%), none of 22, eight of 30 (27%), and eight of 21 (38%) (p=0.001); sustained pain free, one of 26 (4%), none of 22, seven of 30 (23%), and seven of 21 (33%) (p=0.002); recurrence rates, one of five (20%), none of four, four of 15 (27%), and three of 15 (20%). More patients given LY334370 than placebo reported asthenia, somnolence, and dizziness. Interpretation: Our findings show that LY334370 is effective in treatment of acute migraine through selective trigeminovascular neuronal inhibition.
G-protein activation at 5-HT1A receptors by the 5-ht1F ligand LY334370 in guinea-pig brain sections and recombinant cell lines
Br J Pharmacol 1998 May;124(2):283-90.PMID:9641544DOI:10.1038/sj.bjp.0701832.
1. G-protein activation by the 5-ht1F receptor agonist 5-(4-fluorobenzoyl)amino-3-(1-methylpiperidin-4-yl)-1H-indole fumarate (LY334370) was investigated by use of autoradiography of receptor-activated G-proteins in guinea-pig brain sections and [35S]-GTPgammaS binding responses in cell lines stably expressing human 5-HT1A (h 5-HT1A) receptors. 2. LY334370 (10 microM) caused little or no stimulation of [35S]-GTPgammaS binding in guinea-pig brain regions enriched in 5-ht1F binding sites (e.g., claustrum, caudate/putamen and thalamic nuclei), as identified by labelling with 10 nM [3H]-sumatriptan plus 10 nM 5-carboxamidotryptamine (5-CT). 3. Application of LY334370 (10 microM) to guinea-pig brain sections resulted in an increase of [35S]-GTPgammaS binding in hippocampus (123+/-17%), lateral septum (58+/-14%), dorsal raphe (57+/-10%), entorhinal (37+/-11%) and cingulate cortex (28+/-10%). This distribution fits with the G-protein activation mediated by 5-HT1A receptors as found with lisuride (10 microM), and labelling of 5-HT1A receptors by 140 pM [125I]-4-(2'-methoxy-phenyl)- -[2'-(n-2"-pyridinyl)-p-iodobenzamido]-ethyl-piperazine (p-MPPI). 4. The LY334370-mediated [35S]-GTPgammaS response was antagonized by the selective, silent 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohex anecarboxa-mide (WAY100635, 1 microM) in each of the brain structures investigated. The distribution pattern of the [35S]-GTPgammaS binding response and the antagonist profile suggest that the LY334370-induced response in guinea-pig brain is mediated by 5-HT1A receptors. 5. The maximal LY334370-induced [35S]-GTPgammaS binding response (83 to 94%) in membranes of recombinant C6-glial/h 5-HT1A and HeLa/h 5-HT1A cells was close to that of 5-HT, suggesting LY334370 to exert high intrinsic activity at h 5-HT1A receptors. 6. In conclusion, in guinea-pig brain sections and recombinant cell lines the 5-ht1F receptor agonist LY334370 causes G-protein activation that is mediated by 5-HT1A receptors. Caution should be taken when employing this ligand as a putative selective 5-ht1F agonist.