| Size | Price | Stock | Qty |
|---|---|---|---|
| 500mg |
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| 1g |
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| Other Sizes |
| Targets |
Ki: M1 (2.3 nM), M2 (2 nM), M3 (2.5 nM), M4 (2.8 nM), and M5 (2.9 nM)[1]
Muscarinic acetylcholine receptors (mAChRs), specifically M1, M2, M3, M4, and M5 subtypes. (Rac)-5-Hydroxymethyl Tolterodine acts as a non-selective, competitive antagonist at all five mAChR subtypes. |
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| ln Vitro |
The contraction of guinea-pig isolated urinary bladder strips caused by carbachol is competitively and concentration-dependently inhibited in vitro by (Rac)-5-Hydroxymethyl Tolterodine (PNU-200577) (KB of 0.84 nM; pA2 of 9.14)[2].
(Rac)-5-Hydroxymethyl Tolterodine is a potent, non-selective mAChR antagonist with high affinity for all five receptor subtypes. The Ki values are 2.3 nM for M1, 2 nM for M2, 2.5 nM for M3, 2.8 nM for M4, and 2.9 nM for M5 receptors. In functional assays, the compound acts as a competitive antagonist, inhibiting carbachol-induced contractions of isolated guinea pig bladder strips in a concentration-dependent manner with a KB of 0.84 nM and a pA2 of 9.14. These data confirm its potent and efficacious antagonism at mAChRs, consistent with its role as the primary active metabolite of tolterodine. |
| ln Vivo |
Treatment with (Rac)-5-Hydroxymethyl Tolterodine (5-HMT; 0.88 μmol/kg; iv) demonstrates that the drug significantly binds to muscarinic receptors in all organs with the exception of the cerebral cortex, with the bladder exhibiting the longest duration of binding[3].
In vivo, (Rac)-5-Hydroxymethyl Tolterodine (5-HMT; 0.88 μmol/kg; intravenous administration) binds significantly to muscarinic receptors in all organs except the cerebral cortex. The longest duration of binding is observed in the bladder, which is consistent with the therapeutic use of tolterodine for overactive bladder. This tissue distribution pattern explains the clinical efficacy of tolterodine in reducing bladder contractions while minimizing central nervous system side effects. |
| Enzyme Assay |
In vitro receptor binding assays are performed to determine the affinity of (Rac)-5-Hydroxymethyl Tolterodine for the five mAChR subtypes. These assays typically use radioligand binding techniques with membrane preparations from cells or tissues expressing the target receptors. The compound's ability to displace a specific radiolabeled ligand (e.g., [3H]-N-methylscopolamine or [3H]-QNB) from each receptor subtype is measured to calculate its Ki values. Functional antagonism is confirmed by assessing the compound's ability to inhibit agonist-induced responses, such as carbachol-stimulated contractions in isolated tissue preparations.
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| Cell Assay |
In vitro cell-based assays are conducted using cells expressing recombinant mAChR subtypes (e.g., CHO or HEK-293 cells). The cells are treated with a receptor agonist (e.g., carbachol) in the presence or absence of varying concentrations of (Rac)-5-Hydroxymethyl Tolterodine. The inhibition of agonist-induced intracellular signaling, such as calcium mobilization or PI hydrolysis, is measured to quantify the antagonistic activity. The competitive nature of the antagonism is established by assessing the reversal of inhibition at high agonist concentrations. The compound's potency (KB) and affinity (Ki) are determined from these functional and binding assays.
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| Animal Protocol |
In vivo studies are typically conducted in animal models to evaluate the pharmacological effects of (Rac)-5-Hydroxymethyl Tolterodine. The compound is administered via intravenous injection (e.g., 0.88 μmol/kg) to assess its tissue distribution and receptor binding. Its effects on bladder function are evaluated in models of overactive bladder by measuring bladder pressure, contraction frequency, and urine output. The duration of receptor binding in different organs is assessed to understand the tissue selectivity and pharmacokinetic profile of the compound.
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| ADME/Pharmacokinetics |
(Rac)-5-Hydroxymethyl Tolterodine is the primary active metabolite of tolterodine and is responsible for the pharmacological activity of the parent drug. As a metabolite, its pharmacokinetic properties are closely linked to those of tolterodine. Following tolterodine administration, the metabolite is formed rapidly and contributes significantly to the overall antimuscarinic effect. The compound has a LogP of 4.12, indicating moderate lipophilicity. Its tissue distribution is characterized by significant binding to muscarinic receptors in peripheral organs, particularly the bladder, with minimal penetration into the cerebral cortex. This distribution pattern is responsible for the favorable side effect profile of tolterodine, with reduced central nervous system effects compared to other antimuscarinic agents.
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| Toxicity/Toxicokinetics |
No specific toxicity data are publicly available for (Rac)-5-Hydroxymethyl Tolterodine as a standalone compound. However, as the primary active metabolite of tolterodine, its toxicity profile is expected to be similar to that of the parent drug. Tolterodine is generally well-tolerated, with common side effects including dry mouth, constipation, and blurred vision, which are typical of antimuscarinic agents. At high doses, it may cause more severe anticholinergic effects such as urinary retention, tachycardia, and central nervous system disturbances.
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| References |
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| Additional Infomation |
(Rac)-5-Hydroxymethyl Tolterodine is the primary bioactive metabolite of tolterodine, a clinically approved drug for the treatment of overactive bladder. The compound is used as a research tool to study the pharmacology and pharmacokinetics of tolterodine and related antimuscarinic agents. It is also known as (Rac)-Desfesoterodine and (Rac)-PNU-200577. The compound is available as the racemic mixture, and its individual enantiomers may exhibit different pharmacological properties. It is not intended for human therapeutic use as a standalone compound and is strictly for research purposes.
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| Molecular Formula |
C22H31NO2
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|---|---|
| Molecular Weight |
341.49
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| Exact Mass |
341.235
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| CAS # |
200801-70-3
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| Related CAS # |
(Rac)-5-Hydroxymethyl Tolterodine-d14;1185071-13-9;5-Hydroxymethyl Tolterodine-d14 (formate)
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| PubChem CID |
9927971
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| Appearance |
White to off-white solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
490.7±45.0 °C at 760 mmHg
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| Flash Point |
233.2±27.4 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.563
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| LogP |
4.12
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
25
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| Complexity |
357
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)N(CCC(C1=CC=CC=C1)C2=C(C=CC(=C2)CO)O)C(C)C
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| InChi Key |
DUXZAXCGJSBGDW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H31NO2/c1-16(2)23(17(3)4)13-12-20(19-8-6-5-7-9-19)21-14-18(15-24)10-11-22(21)25/h5-11,14,16-17,20,24-25H,12-13,15H2,1-4H3
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| Chemical Name |
2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenol
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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) |
DMSO: 100 mg/mL (292.83 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.32 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 (7.32 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9283 mL | 14.6417 mL | 29.2834 mL | |
| 5 mM | 0.5857 mL | 2.9283 mL | 5.8567 mL | |
| 10 mM | 0.2928 mL | 1.4642 mL | 2.9283 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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