Eptapirone (formerly known as F11440; L0068) is a potent, selective, high efficacy 5-HT1A receptor agonist with marked anxiolytic and antidepressant potential. F 11440 had a higher affinity (pKi, 8.33) for 5-HT1A binding sites than buspirone (pKi, 7.50), but a somewhat lower affinity (pKi, 8.91) than flesinoxan. F 11440 exhibited 4- to 20-fold greater potency in vivo compared to flesinoxan and 30- to 60-fold greater potency compared to buspirone.

Physicochemical Properties

Molecular Formula	C16H23N7O2
Molecular Weight	345.407
Exact Mass	345.19
Elemental Analysis	C, 55.64; H, 6.71; N, 28.39; O, 9.26
CAS #	179756-58-2
Related CAS #	179756-85-5 (fumarate); 179756-58-2
PubChem CID	208928
Appearance	White to off-white solid powder
Density	1.2±0.1 g/cm3
Boiling Point	519.9±60.0 °C at 760 mmHg
Flash Point	268.2±32.9 °C
Vapour Pressure	0.0±1.4 mmHg at 25°C
Index of Refraction	1.563
LogP	-0.34
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	6
Heavy Atom Count	25
Complexity	499
Defined Atom Stereocenter Count	0
SMILES	O=C1N(C([H])([H])[H])C(C([H])=NN1C([H])([H])C([H])([H])C([H])([H])C([H])([H])N1C([H])([H])C([H])([H])N(C2N=C([H])C([H])=C([H])N=2)C([H])([H])C1([H])[H])=O
InChi Key	NMYAHEULKSYAPP-UHFFFAOYSA-N
InChi Code	InChI=1S/C16H23N7O2/c1-20-14(24)13-19-23(16(20)25)8-3-2-7-21-9-11-22(12-10-21)15-17-5-4-6-18-15/h4-6,13H,2-3,7-12H2,1H3
Chemical Name	4-methyl-2-[4-(4-pyrimidin-2-ylpiperazin-1-yl)butyl]-1,2,4-triazine-3,5-dione
Synonyms	Eptapirone free base; Eptapirone; L0068; L-0068; L 0068; F11440; F-11440; F 11440
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
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

Targets	5-HT1A ( pKi = 8.33 )
ln Vitro	Eptapirone has a higher affinity (pKi, 8.33) for 5-HT1A binding sites than buspirone (pKi, 7.50), but a somewhat lower affinity (pKi, 8.91) than flesinoxan. When Eptapirone is added to HeLa cells expressing human 5-HT1A receptors, it reduces the increase in AMP that forskolin causes. Based on its maximal effect, Eptapirone's intrinsic activity is found to be 1.0 in relation to 5-HT, which is significantly higher than that of flesinoxan (0.93), ipsapirone (0.46), and buspirone (0.49). [1]
ln Vivo	In rat pre- and postsynaptic receptors, Eptapirone (F11440) exhibits 4- to 20-fold greater potency than flesinoxan and 30- to 60-fold greater potency than buspirone in terms of 5-HT1A agonist activity (measured, for example, by its ability to decrease hippocampal extracellular serotonin (5-HT) levels and to increase plasma corticosterone levels, respectively). In comparison to buspirone, ipsapirone, and flesinoxan, epopirone produced more significant anxiolytic- and antidepressant-like effects in animal models (increased punished responding in a pigeon conflict procedure and decreased immobility in a rat forced swimming test, respectively). [1]
Cell Assay	DMEM and 10 mM HEPES are preincubated in cells for 10 minutes at room temperature. DMEM, 10 mM HEPES, 100 M forskolin, 100 M IBMX, and suitable vehicle controls are then added to the cells along with drugs at concentrations ranging from 0.1 nM to 100 M. Antagonists are added at the same time as the agonists. Aspirating the medium and adding 0.1 N HCl stops the reaction at the conclusion of the treatment (10 min at room temperature). A commercially available kit is used to measure the cAMP content of cellular extract that has been diluted 1:500 or 1:400 in radioimmunoassay buffer.
Animal Protocol	Rats: F 11440 was suspended in distilled water for in vivo experiments by adding Tween 80 (2 drops/10 ml). F 11440 was dissolved in a 60% PEG and 40% physiological saline mixture before being injected intravenously. Doses are given in terms of the free base's weight. Rats were housed individually in a restricted area that was only accessible by the experimenter twenty-four hours prior to use in the experiments. They were fed 15 g of standard laboratory food, and water was kept freely available. Between 8:00 and 10:30 in the morning, drug treatments were administered to the animals, who were then beheaded and their trunk blood was extracted. When given p.o., F 11440 (or vehicle) was administered 60 minutes before decapitation, and when given i.p., it was administered 30 minutes before decapitation[1].
References	[1]. F 11440, a potent, selective, high efficacy 5-HT1A receptor agonist with marked anxiolytic and antidepressant potential. J Pharmacol Exp Ther. 1998 Oct;287(1):266-83.
Additional Infomation	Eptapirone is a N-arylpiperazine.

Solubility Data

Solubility (In Vitro)

DMSO: 69~250 mg/mL (199.8~723.8 mM) Ethanol: ~39 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.24 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 25.0 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: ≥ 2.5 mg/mL (7.24 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 25.0 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: ≥ 2.5 mg/mL (7.24 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 25.0 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	2.8951 mL	14.4756 mL	28.9511 mL
	5 mM	0.5790 mL	2.8951 mL	5.7902 mL
	10 mM	0.2895 mL	1.4476 mL	2.8951 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.