Repinotan (BAY x 3702 free base) is a specific, BBB (blood-brain barrier) permeable (penetrable), and orally bioactive 5-HT1A receptor agonist/activator with a Ki of 0.19 nM (calf hippocampus), 0.25 nM (rat and human cortex) and 0.59 nM (rat hippocampus). Repinotan has weaker affinity for other related receptors. Repinotan has potent neuro-protection effects.

Physicochemical Properties

Molecular Formula	C21H24N2O4S
Molecular Weight	400.49
Exact Mass	400.146
CAS #	144980-29-0
Related CAS #	Repinotan hydrochloride;144980-77-8
PubChem CID	198757
Appearance	Typically exists as solid at room temperature
Density	1.284g/cm3
Boiling Point	599.5ºC at 760 mmHg
Flash Point	316.4ºC
Vapour Pressure	2.49E-14mmHg at 25°C
Index of Refraction	1.603
LogP	4.004
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	7
Heavy Atom Count	28
Complexity	647
Defined Atom Stereocenter Count	1
SMILES	C1=CC=C2C(=C1)CC[C@H](CNCCCCN3C(=O)C4=CC=CC=C4S3(=O)=O)O2
InChi Key	YGYBFMRFXNDIPO-QGZVFWFLSA-N
InChi Code	InChI=1S/C21H24N2O4S/c24-21-18-8-2-4-10-20(18)28(25,26)23(21)14-6-5-13-22-15-17-12-11-16-7-1-3-9-19(16)27-17/h1-4,7-10,17,22H,5-6,11-15H2/t17-/m1/s1
Chemical Name	2-[4-[[(2R)-3,4-dihydro-2H-chromen-2-yl]methylamino]butyl]-1,1-dioxo-1,2-benzothiazol-3-one
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 Receptor 0.19 nM (Ki, In calf hippocampus) 5-HT1A Receptor 0.25 nM (Ki, In rat and human cortex) 5-HT1A Receptor 0.59 nM (Ki, In rat hippocampus) 5-HT7 Receptor 6 nM (Ki)
ln Vitro	5-HT7 (Ki = 6 nM), α1- and α2 adrenergic (Ki = 6 nM and 7 nM, respectively), 5-HT1D (36 nM), dopamine D2 and D4 (48 nM and 91 nM, respectively), σ sites (176 nM), and 5-HT2C (310 nM) receptors are among those to which repinotan binds with a lesser affinity[1]. Rat cortical and hippocampus neurons in vitro are shielded against apoptosis caused by 25 nM staurosporine by exposure to repinotan. Repinotan inhibits the release of lactate dehydrogenase, DNA fragmentation, and poptotic body formation following staurosporine-induced apoptosis in a concentration-dependent manner, ranging from 50 pM to 1 μM[1].
ln Vivo	In the paradigms of permanent middle cerebral artery blockage, temporary middle cerebral artery occlusion, and traumatic brain injury, repinotan (1–100 μg/kg) significantly reduces infarcts in a dose-dependent manner[1]. Repinotan has a brief half-life in plasma (t1/2 = 0.6 h in rats and 0.4 h in rhesus monkeys), and it undergoes significant metabolism[1].
References	[1]. A C Berends, et al. A review of the neuroprotective properties of the 5-HT1A receptor agonist repinotan HCl (BAYx3702) in ischemic stroke. CNS Drug Rev. Winter 2005;11(4):379-402.
Additional Infomation	Repinotan is a high-affinity, selective, full agonist of the 5HT1A-receptor subtype with neuroprotective properties. Drug Indication Investigated for use/treatment in strokes, cerebral ischemia, and depression. Mechanism of Action Repinotan is a 5-HT1A receptor agonist which inhibits glutamate induced depolarization. The effect of repinotan in neuronal cells has been reported to be mediated by a variety of mechanisms/signaling pathways, including activation of the anti-apoptotic phosphatidylinositol 3-kinase (PI-3K) pathway, inhibition of glutamate release (probably via opening of K+ channels leading to membrane hyperpolarization), extracellular-regulated kinase (Erk)-stimulated Bcl-2 expression or inhibition of caspase-3 activity, and increased release of the neurite extension factor S-100 beta.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.4969 mL	12.4847 mL	24.9694 mL
	5 mM	0.4994 mL	2.4969 mL	4.9939 mL
	10 mM	0.2497 mL	1.2485 mL	2.4969 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.