| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
M1 Muscarinic Acetylcholine Receptors (mAChR) and L-type Calcium Channels (Caᵥ1.2). Terodiline HCl is an M1-selective mAChR antagonist with Kb values of 15 nM (M1), 160 nM (M2, cardiac), and 198-280 nM (M3, bladder/ileum). It also blocks L-type voltage-dependent calcium channels (Ca2+ channels) in smooth muscle. By blocking both muscarinic receptors (particularly M3 receptors in the bladder) and calcium channels, it inhibits detrusor muscle contraction, reduces intravesical pressure, and increases bladder capacity, thereby reducing urinary frequency and urgency.
|
|---|---|
| ln Vitro |
Terodiline HCl exhibits high affinity for the M1 muscarinic receptor (Kb = 15 nM) and weaker affinity for M2 (Kb = 160 nM) and M3 (Kb = 198-280 nM) receptors in rabbit tissue preparations. The compound blocks carbachol-induced contractions of isolated guinea pig bladder and ileum (M3-mediated) in a non-competitive manner. It also blocks calcium-induced contractions of depolarized rat aorta (calcium channel blockade), with an IC50 of approximately 1-5 microM. It has a slight preference for M1 over M3 receptors in functional assays.
|
| ln Vivo |
Trodiline (80 mg/kg; SC) has a comparable effect on pupil diameter (ED50 = 59 mg/kg) and reduces intravesical bladder pressure and carbachol-induced salivation (ID50 = 24 and 35 mg/kg, respectively) [1].
Terodiline (80 mg/kg subcutaneous) produces a comparable effect on pupil diameter (ED50 = 59 mg/kg, mydriasis via M3 blockade) and reduces intravesical bladder pressure and carbachol-induced salivation (ID50 = 24 and 35 mg/kg, respectively) in guinea pigs. It inhibits bladder contractions in anesthetized dogs and cats, increasing bladder capacity without completely blocking voiding. In animal models of urinary incontinence, terodiline reduces the frequency of non-voiding contractions (instability) and increases the volume threshold for micturition. |
| Enzyme Assay |
Muscarinic receptor binding affinity is assessed in radioligand binding assays using membrane preparations from rabbit tissues: vas deferens (M1), atria (M2), bladder and ileum (M3). Membranes (50-100 microg protein) are incubated with [3H]N-methylscopolamine ([3H]NMS) as the radioligand (non-selective mAChR antagonist) and varying concentrations of Terodiline HCl (0.1-1000 nM) in 50 mM phosphate buffer pH 7.4 for 60-90 minutes at 25degC. Nonspecific binding is determined with 10 microM atropine. Bound radioactivity is separated by filtration through GF/B filters and measured by liquid scintillation. Kb values are calculated from Schild analysis or inhibition curves.
|
| Cell Assay |
Isolated guinea pig bladder detrusor strips (2 × 10 mm) are mounted vertically in organ baths containing Krebs solution (37degC, 95% O2/5% CO2) at a resting tension of 0.5-1 g. After stabilization (60 min), cumulative concentration-response curves to carbachol (CCh, 10-⁹ to 10-⁵ M, a muscarinic agonist) are generated in the absence or presence of Terodiline HCl (0.1-10 microM, 30 min pre-incubation). Contractile force is recorded isometrically. The EC50 of CCh is calculated, and the rightward shift is analyzed. For calcium channel blockade, rat aortic rings are depolarized with 60 mM KCl in Ca2+-free Krebs buffer to induce tonic contraction. After stabilization, cumulative CaCl2 (0.1-10 mM) is added to generate a calcium concentration-response curve in the presence or absence of Terodiline.
|
| Animal Protocol |
Animal/Disease Models: Female or male Hartley guinea pig (200-600 g) [1]
Doses: 80 mg/kg Route of Administration: subcutaneous injection Experimental Results: Generated an ID50 of 24±6 mg/kg. Higher doses are fatal. Male Hartley guinea pigs (200-600 g) are anesthetized, and a catheter is inserted into the bladder for intravesical pressure monitoring (cystometry). Terodiline (80 mg/kg) or vehicle is administered subcutaneously. The bladder is filled with warm saline at a constant rate, and the micturition reflex is triggered. The ID50 (dose producing 50% inhibition of intravesical pressure) is calculated. In the carbachol-induced salivation model: guinea pigs are anesthetized, and salivary secretion is stimulated by carbachol (0.2 mg/kg, s.c.). Terodiline (10-100 mg/kg) is administered 30 min prior. Saliva is collected from the mouth with pre-weighed cotton balls over 30 min. The amount of saliva is weighed, and the ID50 (50% inhibition of salivation) is calculated. High doses (≥80 mg/kg) are lethal. |
| ADME/Pharmacokinetics |
Terodiline HCl is well absorbed orally (>80%), highly lipophilic (logP ≈ 4.5), and undergoes extensive hepatic metabolism (CYP2D6). The terminal half-life is long, approximately 60 hours in humans, contributing to accumulation and toxicity. It crosses the blood-brain barrier (BBB). The calcium channel blocking activity adds to its smooth muscle relaxant effect but also contributes to its cardiac toxicity.
|
| Toxicity/Toxicokinetics |
The major dose-limiting toxicity of terodiline is cardiac arrhythmia, specifically Torsade de Pointes (polymorphic ventricular tachycardia) due to hERG (IKr) potassium channel blockade (QT prolongation). This led to its worldwide withdrawal in 1991. Other adverse effects include anticholinergic side effects: dry mouth, constipation, blurred vision, urinary retention, and tachycardia. Central nervous system effects (drowsiness, confusion) can occur.
|
| References | |
| Additional Infomation |
Tardelineate hydrochloride is a diarylmethane.
Terodiline HCl is an M1-selective muscarinic receptor antagonist and a calcium channel blocker. It was marketed under the brand name Mictrol (US) and Micturin (Europe) for overactive bladder but was withdrawn in 1991 due to QT prolongation and risk of Torsade de Pointes, which was fatal in some patients. Terodiline is now a research tool for studying muscarinic receptor pharmacology and calcium channel modulation in smooth muscle and for investigating the mechanisms of drug-induced QT prolongation (hERG liability). It is not available as a prescription drug. |
| Molecular Formula |
C20H27N.HCL
|
|---|---|
| Molecular Weight |
317.89602
|
| Exact Mass |
317.191
|
| Elemental Analysis |
C, 75.56; H, 8.88; Cl, 11.15; N, 4.41
|
| CAS # |
7082-21-5
|
| Related CAS # |
Terodiline;15793-40-5
|
| PubChem CID |
23479
|
| Appearance |
White to off-white solid powder
|
| Boiling Point |
390.9ºC at 760 mmHg
|
| Flash Point |
168.9ºC
|
| LogP |
6.178
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
1
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
22
|
| Complexity |
261
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC(CC(C1=CC=CC=C1)C2=CC=CC=C2)NC(C)(C)C.Cl
|
| InChi Key |
RNGHAJVBYQPLAZ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C20H27N.ClH/c1-16(21-20(2,3)4)15-19(17-11-7-5-8-12-17)18-13-9-6-10-14-18;/h5-14,16,19,21H,15H2,1-4H3;1H
|
| Chemical Name |
N-tert-butyl-4,4-diphenylbutan-2-amine;hydrochloride
|
| Synonyms |
TERODILINE HYDROCHLORIDE; 7082-21-5; Bicor; DTXSID1048968; K2ZA89W43F;
|
| 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 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)
|
| Solubility (In Vitro) |
DMSO: ~40 mg/mL (125.8 mM)
|
|---|---|
| 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 | 3.1456 mL | 15.7282 mL | 31.4564 mL | |
| 5 mM | 0.6291 mL | 3.1456 mL | 6.2913 mL | |
| 10 mM | 0.3146 mL | 1.5728 mL | 3.1456 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
