LY310762 is a selective 5-HT1D receptor blocker (antagonist) (Ki=249 nM) with weak affinity for 5-HT1B receptors. LY310762 can effectively abrogate the renal vasodilatory effects of 5-HT. LY310762 also significantly, but not completely, blocks the Sumatriptan induced decrease in excitatory postsynaptic potential (EPSC) amplitude.

Physicochemical Properties

Molecular Formula	C24H28CLFN2O2
Molecular Weight	430.94
Exact Mass	430.182
CAS #	192927-92-7
PubChem CID	11957576
Appearance	White to off-white solid powder
LogP	4.849
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	5
Heavy Atom Count	30
Complexity	606
Defined Atom Stereocenter Count	0
SMILES	Cl[H].FC1C([H])=C([H])C(=C([H])C=1[H])C(C1([H])C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])N2C3=C([H])C([H])=C([H])C([H])=C3C(C([H])([H])[H])(C([H])([H])[H])C2=O)C([H])([H])C1([H])[H])=O
Synonyms	LY-310762; LY 310762; LY310762
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	In guinea pig cortical slices, LY310762 (0.01-1 µM) exhibits potassium-induced increase of [3H]5-HT efflux, with an EC50 value of 31 nM [1]. The decrease in excitatory postsynaptic potential (EPSC) caused by sumatriptan is largely, albeit not fully, blocked by LY310762 (10 µM) [3].
ln Vivo	Fluoxetine, a selective serotonin reuptake inhibitor, produces extracellular 5-HT concentrations in vivo. LY310762 (10 mg/kg; i.p.; single dose) greatly boosts these concentrations [1]. In a rat model of phenylephrine infusion, LY310762 (1 mg/kg; intravenous injection; single dosage) completely eliminates the vasodilatory effects of 5-HT [2].
Animal Protocol	Animal/Disease Models: Dunkin Hartley guinea pig (female; 350-400 g, Harlan) [1]. Doses: 10 mg/kg Route of Administration: intraperitoneal (ip) injection; Single Experimental Results:Further significant enhancement of 5-HT response to fluoxetine. Animal/Disease Models: Male Wistar rat (270-330 g; phenylephrine infusion rat model) [2]. Doses: 1 mg/kg Route of Administration: intravenous (iv) (iv)injection; Single Experimental Results:Complete elimination of the vasodilatory effect of 5-HT.
References	[1]. The role of the 5-HT1D receptor as a presynaptic autoreceptor in the guinea pig. Eur J Pharmacol. 2004 Jun 16;493(1-3):85-93. [2]. Pharmacological evidence that 5-HT1D activation induces renal vasodilation by NO pathway in rats. Clin Exp Pharmacol Physiol. 2015 Jun;42(6):640-7. [3]. Choi IS, Cho JH, An CH, Jung JK, Hur YK, Choi JK, Jang IS. 5-HT(1B) receptors inhibit glutamate release from primary afferent terminals in rat medullary dorsal horn neurons. Br J Pharmacol. 2012 Sep;167(2):356-67.
Additional Infomation	LY-310762 hydrochloride is a hydrochloride resulting from the formal reation of equimolar amount of LY-310762 with hydrogen chloride. A potent and selective antagonist for the 5-hydroxytryptamine 1D (5-HT1D) receptor. It has a role as a receptor modulator and a serotonergic antagonist. It contains a LY-310762(1+).

Solubility Data

Solubility (In Vitro)

DMSO : ~18.33 mg/mL (~42.53 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.83 mg/mL (4.25 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 18.3 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.83 mg/mL (4.25 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 18.3 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 1.83 mg/mL (4.25 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 18.3 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.3205 mL	11.6025 mL	23.2051 mL
	5 mM	0.4641 mL	2.3205 mL	4.6410 mL
	10 mM	0.2321 mL	1.1603 mL	2.3205 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.