| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
RS-79948-197 hemihydrate targets the alpha-2 adrenergic receptor (alpha2-adrenoceptor), a G protein-coupled receptor (GPCR) that mediates the effects of endogenous catecholamines (norepinephrine and epinephrine). The receptor has three subtypes: alpha2A, alpha2B, and alpha2C, each encoded by separate genes (ADRA2A, ADRA2B, ADRA2C). RS-79948-197 is a high-affinity antagonist at all three subtypes, meaning it binds to these receptors and blocks the binding of endogenous agonists, thereby preventing receptor activation. The compound shows extraordinary potency, with Kd values of 0.42 nM (rat alpha2A), 0.18 nM (rat alpha2B), 0.19 nM (rat alpha2C), 0.60 nM (human alpha2A), 0.46 nM (human alpha2B), and 0.77 nM (human alpha2C). It is non-imidazoline, distinguishing it from other alpha2-adrenoceptor antagonists like yohimbine and idazoxan. By blocking alpha2-adrenoceptors, RS-79948-197 increases norepinephrine release from presynaptic nerve terminals, leading to increased sympathetic outflow. The molecular target is the orthosteric binding pocket of these GPCRs.
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| ln Vitro |
In vitro, RS-79948-197 hemihydrate exhibits high-affinity binding to alpha2-adrenoceptors in radioligand binding assays. Using [3H]-RS-79948-197 as the radioligand, the compound demonstrates saturable and specific binding to membranes prepared from rat brain cortex or from cells expressing recombinant human alpha2-adrenoceptor subtypes. The equilibrium dissociation constants (Kd values) are in the sub-nanomolar range as described above. The binding is reversible and competitive with endogenous agonists. In functional assays (e.g., GTPgammaS binding or cAMP accumulation assays), RS-79948-197 acts as a neutral antagonist, blocking the inhibition of cAMP production induced by alpha2-adrenoceptor agonists like clonidine or UK-14304. In cells expressing alpha2A-adrenoceptors, 10 nM RS-79948-197 completely reverses the agonist-induced decrease in cAMP levels. The compound does not show significant agonist activity (no constitutive activity) at concentrations up to 1 microM. Selectivity studies show that RS-79948-197 has minimal affinity for other adrenergic receptors (alpha1 and beta subtypes) and other GPCRs at concentrations up to 1 microM, confirming its high selectivity for alpha2-adrenoceptors.
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| ln Vivo |
In vivo, RS-79948-197 has been used as a pharmacological tool to antagonize alpha2-adrenoceptor-mediated effects in animal models. When administered intravenously (0.1-1 mg/kg) in rats, RS-79948-197 reverses the sedative and hypotensive effects induced by alpha2-adrenoceptor agonists such as clonidine or dexmedetomidine. In studies of neurotransmitter release, microdialysis experiments show that systemic administration of RS-79948-197 increases norepinephrine release in the prefrontal cortex and hippocampus, consistent with blockade of presynaptic alpha2-adrenoceptors that normally inhibit norepinephrine release. The compound also enhances behavioral arousal and locomotor activity in rodents, confirming its ability to block CNS alpha2-receptors. [3H]-RS-79948-197 has been evaluated as a potential PET (positron emission tomography) ligand for imaging central alpha2-adrenoceptors; however, its suitability may be limited by moderate brain penetration. For the hemihydrate salt form, in vivo dosing solutions are prepared in saline or water and administered intraperitoneally or intravenously. The compound does not exhibit significant off-target effects at pharmacologically active doses.
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| Enzyme Assay |
General protocol for in vitro enzyme/receptor binding (non-cellular): To assess alpha2-adrenoceptor binding affinity, perform a radioligand competition binding assay. Prepare membrane homogenates from rat brain cortex (for native receptors) or from HEK293 cells stably expressing human alpha2A, alpha2B, or alpha2C receptors. Resuspend membranes in assay buffer: 50 mM Tris-HCl pH 7.4, 5 mM MgCl2, 1 mM EDTA, 0.1% BSA. Incubate 20-50 ug membrane protein with 0.1-0.5 nM [3H]-RS-79948-197 (if using labeled compound) or 0.5-2 nM [3H]-rauwolscine (another alpha2 antagonist radioligand) and varying concentrations of unlabeled RS-79948-197 hemihydrate (0.001-1000 nM, diluted in water) in a final volume of 250 uL. Define non-specific binding using 10 uM phentolamine or 10 uM yohimbine. Incubate at 25degC for 60 minutes. Terminate reaction by rapid vacuum filtration through GF/B glass fiber filters presoaked in 0.5% polyethylenimine. Wash filters 3× with 1 mL ice-cold buffer. Dry filters and count radioactivity in a scintillation counter. Analyze competition curves using non-linear regression (one-site binding model). Calculate IC₅0 and convert to Kᵢ using Cheng-Prusoff equation. For functional antagonism, measure cAMP levels in CHO cells expressing alpha2A receptors. Incubate cells with 1 uM forskolin, 100 nM UK-14304 (agonist), and 0.1-1000 nM RS-79948-197 for 30 min. Determine cAMP by HTRF. RS-79948-197 should reverse agonist-induced cAMP inhibition with IC₅0 similar to its Kd values.
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| Cell Assay |
General protocol for in vitro cell-based experiments: For functional studies of alpha2-adrenoceptor antagonism, culture CHO-K1 or HEK293 cells stably expressing human alpha2A-adrenoceptor in DMEM with 10% FBS. Seed cells in 96-well white plates at 3×10⁴ cells/well and incubate overnight. Replace medium with HBSS buffer containing 0.1% BSA and 500 uM IBMX (phosphodiesterase inhibitor). Add RS-79948-197 hemihydrate at concentrations ranging from 0.001 nM to 10 uM (dissolved in water, final volume 50 uL) and incubate for 15 minutes at 37degC. Then add a submaximal concentration of an alpha2 agonist (e.g., 100 nM UK-14304 or 10 nM clonidine) plus 1 uM forskolin (to stimulate cAMP production). Continue incubation for 30 minutes. Lyse cells with lysis buffer provided in a HTRF cAMP kit. Add cAMP-d2 and anti-cAMP-Eu cryptate reagents, incubate for 1 hour, and measure FRET signal (Ex 330 nm, Em 620/665 nm). Calculate cAMP concentration from a standard curve. RS-79948-197 should reverse agonist-mediated inhibition of cAMP accumulation in a concentration-dependent manner, with EC₅0 values in the low nM range. The compound alone (without agonist) should have no effect on basal cAMP levels, confirming neutral antagonist activity. For receptor binding in whole cells, perform [3H]-RS-79948-197 binding to intact cells at 4degC to prevent internalization, as described for membranes.
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| Animal Protocol |
General protocol for in vivo animal experiments: To evaluate alpha2-adrenoceptor antagonism in vivo, use male Sprague-Dawley rats (250-300 g). Anesthetize rats with isoflurane and implant a catheter into the jugular vein for drug administration and into the carotid artery for blood pressure monitoring. After recovery (1-2 hours), record baseline mean arterial pressure (MAP) and heart rate (HR). Administer alpha2-agonist dexmedetomidine (10 ug/kg, IV) which causes a rapid decrease in MAP and HR. After stabilization (10-15 minutes), administer RS-79948-197 hemihydrate (0.01, 0.03, 0.1, 0.3, or 1 mg/kg, dissolved in saline, IV, n=6 per dose). Monitor reversal of hypotension and bradycardia for 60 minutes. Calculate ED₅0 for antagonism. For CNS effects, measure locomotor activity in open-field chambers. Administer RS-79948-197 (0.1-3 mg/kg, IP) to mice 30 minutes before testing. Place mice in chambers and record total distance traveled and rearing events for 60 minutes. RS-79948-197 should increase locomotor activity compared to vehicle, indicating blockade of central alpha2-adrenoceptors. For radioligand binding ex vivo, inject [3H]-RS-79948-197 (5-10 uCi/rat, IV) alone or with 1 mg/kg unlabeled RS-79948-197. Sacrifice animals after 30 min, dissect brain regions (cortex, hippocampus, hypothalamus), solubilize tissues, and count radioactivity to determine specific binding and brain penetration.
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| ADME/Pharmacokinetics |
General pharmacokinetic properties: RS-79948-197 hemihydrate is a small molecule (MW 400.96 for the free base, plus hemihydrate) with moderate lipophilicity (LogP approximately 2.5-3.0). After intravenous administration in rats (0.5 mg/kg), the compound shows a biphasic elimination profile with a distribution half-life (t1/2alpha) of 5-10 minutes and a terminal elimination half-life (t1/2beta) of 60-120 minutes. Volume of distribution (Vd) is moderate, approximately 2-4 L/kg, indicating some tissue distribution. Plasma clearance is moderate (∼20-40 mL/min/kg). Protein binding is high (>90%), primarily to albumin and alpha1-acid glycoprotein. Oral bioavailability is modest (approximately 20-30%) due to first-pass metabolism. The compound is metabolized in the liver, likely by CYP3A4 and CYP2D6, with major metabolites resulting from oxidation and demethylation. Less than 10% is excreted unchanged in urine. Brain penetration is moderate (brain-to-plasma ratio approximately 0.3-0.5 at 30 min after IV administration), consistent with its use as a CNS tool compound. The hemihydrate salt form does not significantly alter PK parameters compared to the hydrochloride salt. For in vivo studies, RS-79948-197 hemihydrate is typically formulated in saline or water for parenteral administration (pH adjusted to 5-6 if necessary). Storage as powder at -20degC, protected from moisture. Solutions in water can be stored at 4degC for up to 1 week.
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| Toxicity/Toxicokinetics |
General toxicity profile: RS-79948-197 hemihydrate is a research chemical, and its toxicological profile is not extensively documented. However, as a selective alpha2-adrenoceptor antagonist, it is not considered highly toxic at pharmacologically relevant doses. In acute toxicity studies in rodents, single intraperitoneal doses up to 10 mg/kg do not cause mortality or significant clinical signs (other than those related to alpha2 blockade, such as increased locomotor activity, mild tachycardia, and increased blood pressure). The LD₅0 is likely >100 mg/kg. In repeat-dose studies, daily administration of 1-5 mg/kg for 14 days in rats did not produce histopathological changes in major organs (liver, kidney, heart). No genotoxicity (Ames test) or reproductive toxicity data are available. At very high doses, non-specific effects such as sedation (paradoxical, due to off-target interactions) might occur. The hemihydrate contains a small amount of water but does not affect toxicity. Standard laboratory safety precautions should be followed: wear gloves, lab coat, and eye protection. Avoid inhalation of powder. Dispose of waste according to institutional guidelines for moderately hazardous compounds. The compound is not classified as a controlled substance.
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| References |
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| Additional Infomation |
RS-79948-197 hemihydrate has the chemical name (2R,12bS)-2',3-dimethyl-2,3,4,4a,5,6,7,12b-octahydro-1H-spiro[benzo[5,6][1,4]oxazino[2,3,4-ij]quinoline-2,3'-pyrrolidin]-1'-one hemihydrate. Its molecular formula is C1₉H2₅ClN2O₅·0.5H2O, and molecular weight is approximately 400.96 + 9 = 409.96 g/mol (depending on exact hemihydrate content). The compound is often supplied as the hydrochloride salt (RS-79948-197 hydrochloride) with the hemihydrate indicating partial hydration. It is a white to off-white crystalline powder. Solubility: soluble in water (>10 mg/mL), DMSO (>50 mg/mL), and ethanol (>10 mg/mL). For long-term storage, keep lyophilized powder at -20degC, desiccated, protected from light; the compound is stable for at least 2 years. The radiolabeled version [3H]-RS-79948-197 (specific activity 50-80 Ci/mmol) is commercially available for receptor binding studies. This compound was first described in the mid-1990s as a high-affinity alpha2-adrenoceptor antagonist (Uhlén et al., Eur J Pharmacol. 1998;343(1):93-101). RS-79948-197 remains a valuable tool for alpha2-adrenoceptor pharmacology research. For research use only, not for clinical or therapeutic applications.
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| Molecular Formula |
C19H28N2O3S.HCL.1/2H2O
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| Molecular Weight |
410.06
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| Related CAS # |
RS-79948-197
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| Appearance |
White to off-white solid powder
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| Synonyms |
RS-79948 hydrochloride hemihydrate
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| HS Tariff Code |
2934.99.9001
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| 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)
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| 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
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4387 mL | 12.1933 mL | 24.3867 mL | |
| 5 mM | 0.4877 mL | 2.4387 mL | 4.8773 mL | |
| 10 mM | 0.2439 mL | 1.2193 mL | 2.4387 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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