| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
L-Hyoscyamine-d3 acts as a potent and competitive antagonist at muscarinic acetylcholine receptors (mAChRs), specifically targeting M1 through M5 subtypes and showing notable selectivity for the M2 subtype.
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as tracers for quantification throughout the drug development process. Due to its potential to alter the pharmacokinetic and metabolic characteristics of medications, deuteration has drawn attention[1].
As a deuterated analog, L-Hyoscyamine-d3 retains the receptor binding characteristics of its parent compound. It exerts its biological effects by blocking muscarinic receptors in various tissues. |
| ln Vivo |
In vivo studies indicate that the parent compound L-hyoscyamine is rapidly absorbed after oral administration with a tmax of 1-2 hours and undergoes extensive first-pass metabolism. The compound primarily functions as an anticholinergic agent.
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| Enzyme Assay |
Non-cell assays typically involve competitive radioligand binding experiments using membrane preparations expressing specific muscarinic receptor subtypes. Membranes are incubated with varying concentrations of L-Hyoscyamine-d3 and a fixed concentration of a radiolabeled antagonist such as [3H]-N-methylscopolamine. Following incubation at room temperature for 60-90 minutes, bound and free radioligands are separated by rapid filtration through glass fiber filters, and radioactivity is measured by liquid scintillation counting to determine Ki values.
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| Cell Assay |
Cell-based assays utilize cell lines such as CHO-K1 cells stably transfected with individual muscarinic receptor subtypes. Cells are seeded in multi-well plates and grown to confluence. To measure functional antagonism, intracellular calcium mobilization (for M1, M3, M5) or cAMP accumulation (for M2, M4) is assessed. Cells are pre-incubated with L-Hyoscyamine-d3 (typically 1 nM to 10 uM) for 15-30 minutes prior to stimulation with a muscarinic agonist (e.g., carbachol). The reduction in agonist-induced signal is measured using fluorescent calcium indicators or homogeneous time-resolved fluorescence (HTRF) cAMP detection kits.
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| Animal Protocol |
In vivo protocols in rodents typically involve administration by oral gavage or intraperitoneal injection at doses ranging from 0.1 to 10 mg/kg. The compound is used to study its effects on gastric emptying, salivation, and intestinal transit. Blood samples are collected at predetermined time points (0, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose) and plasma is separated for LC-MS/MS analysis to determine deuterated drug concentrations. Tissues including brain, heart, and liver are harvested for biodistribution studies.
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| ADME/Pharmacokinetics |
The pharmacokinetics of the parent compound L-hyoscyamine in humans shows rapid absorption with an oral bioavailability of less than 20% due to extensive first-pass metabolism. The volume of distribution is approximately 2-3 L/kg, reflecting extensive tissue distribution including the central nervous system. Plasma protein binding is moderate (approximately 50%). The elimination half-life is approximately 3-5 hours. Metabolism occurs primarily via hydrolysis and CYP3A4-mediated oxidation. The deuterated version is expected to show altered metabolic stability and potentially improved pharmacokinetic properties compared to the non-deuterated parent compound.
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| Toxicity/Toxicokinetics |
The non-deuterated parent L-hyoscyamine has been used clinically as an antispasmodic and antisecretory agent, with reported adverse effects including dry mouth, blurred vision, urinary retention, constipation, and central nervous system effects such as confusion and agitation at higher doses. The acute oral LD50 in rodents is approximately 1,000-1,500 mg/kg. Deuteration may affect the toxicity profile by altering the metabolic pathway and potentially reducing the formation of toxic metabolites, though the specific toxicity data for the deuterated form are not extensively documented.
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| References |
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| Additional Infomation |
L-Hyoscyamine-d3 is primarily used as an internal standard for the quantification of L-hyoscyamine in biological samples by mass spectrometry-based analytical methods. Non-deuterated L-hyoscyamine is also known as daturine and is one of the two enantiomers that make up atropine, the other being D-hyoscyamine. Ongoing clinical trials are evaluating various deuterated compounds for human diseases, with deuteration potentially redirecting metabolic pathways to reduce toxicities or improve pharmacokinetic profiles.
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| Molecular Formula |
C17H20D3NO3
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|---|---|
| Molecular Weight |
292.39
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| Related CAS # |
L-Hyoscyamine;101-31-5
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| Appearance |
White to off-white solid powder
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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 |
| 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 | 3.4201 mL | 17.1004 mL | 34.2009 mL | |
| 5 mM | 0.6840 mL | 3.4201 mL | 6.8402 mL | |
| 10 mM | 0.3420 mL | 1.7100 mL | 3.4201 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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