| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Demeclocycline calcium exerts its antibacterial effect by binding to the 30S subunit of the bacterial ribosome, preventing the binding of aminoacyl-tRNA to the mRNA-ribosome complex, thereby inhibiting bacterial protein synthesis . This mechanism is primarily bacteriostatic. In mammalian systems, demeclocycline affects the cyclic AMP (cAMP) second messenger system in rat brain by reducing noradrenaline-stimulated cAMP formation in cortical slices, an effect attributed to the Ca²⁺-chelating ability of tetracyclines rather than direct adenylate cyclase inhibition . Additionally, demeclocycline inhibits the action of vasopressin (antidiuretic hormone) on renal collecting tubules, leading to nephrogenic diabetes insipidus and diuresis .
The primary targets are the bacterial 30S ribosomal subunit and the vasopressin receptor in renal tubules. Demeclocycline binds to the 30S ribosomal subunit and prevents binding of aminoacyl-tRNA to the mRNA-ribosome complex, thereby inhibiting protein synthesis. It also inhibits the effect of vasopressin on the renal tubules, causing diuresis. It is a tetracycline analog with a 7-chloro and 6-methyl substitution. |
|---|---|
| ln Vitro |
In vitro studies have demonstrated that demeclocycline exhibits broad-spectrum antibacterial activity against a wide range of Gram-positive and Gram-negative bacteria, including Bacillus anthracis, Listeria monocytogenes, Staphylococcus aureus, Streptococcus pneumoniae, Neisseria gonorrhoeae, Haemophilus influenzae, Vibrio cholerae, Yersinia pestis, Francisella tularensis, Brucella species, Rickettsiae, Chlamydia trachomatis, Mycoplasma pneumoniae, and Treponema pallidum . In rat brain cortical slices, demeclocycline (10-1000 µM) dose-dependently reduces noradrenaline-stimulated cAMP formation and inhibits ouabain-stimulated cAMP accumulation . Stability studies of Ledermix® Paste show that demeclocycline calcium (as the hydrochloride equivalent) has an initial concentration of 3.0% in the paste formulation .
Demeclocycline calcium is an orally active tetracycline antibiotic. It inhibits the binding of aminoacyl tRNA by binding to the 30S ribosomal subunit, thereby affecting protein synthesis. It also inhibits the effect of vasopressin on the renal tubules, thereby causing diuresis. It is excreted more slowly than tetracycline, maintaining effective blood levels for longer periods. |
| ln Vivo |
In vivo, demeclocycline is clinically used for the treatment of various bacterial infections including Rocky Mountain spotted fever, typhus, Q fever, mycoplasmal pneumonia, psittacosis, trachoma, brucellosis (with streptomycin), tularemia, plague, cholera, and as adjunctive therapy in severe acne . It is also indicated for penicillin-allergic patients for the treatment of syphilis, yaws, listeriosis, and anthrax . One of its unique uses is the treatment of hyponatremia due to the syndrome of inappropriate antidiuretic hormone (SIADH) when fluid restriction alone is ineffective . In dental applications, demeclocycline calcium is used in Ledermix® Paste for endodontic treatment. Studies show that when mixed with calcium hydroxide powder, the concentration of demeclocycline calcium decreases by 80% over 7 days, while mixing with Pulpdent® (calcium hydroxide paste) results in only a 19% loss over the same period .
In vivo, demeclocycline is used as an antibiotic and for the treatment of SIADH (syndrome of inappropriate antidiuretic hormone secretion). It inhibits vasopressin action in renal tubules, causing diuresis. Typical antibiotic doses range from 150-300 mg administered orally every 6-12 hours. It is excreted more slowly than tetracycline. |
| Enzyme Assay |
Methodology for cAMP Assay in Rat Brain Cortical Slices: To investigate the effects of demeclocycline on the cAMP second messenger system, rat brain cortical slices are pre-incubated with various concentrations of demeclocycline (10-1000 µM) in Krebs-Ringer bicarbonate buffer containing glucose and 0.1% bovine serum albumin, gassed with 95% O₂/5% CO₂ at 37°C for 15 minutes . Slices are then stimulated with noradrenaline (100 µM), forskolin (10 µM), or ouabain (1 mM) for 10 minutes. The reaction is terminated by adding trichloroacetic acid (final concentration 5%) and homogenization. After centrifugation, the supernatant is extracted with water-saturated diethyl ether to remove TCA. Cyclic AMP is measured by a specific radioimmunoassay or protein binding assay, and results are expressed as pmol cAMP/mg protein .
Non-cell assays for demeclocycline include bacterial ribosome binding assays using purified 30S subunits. The compound is incubated with ribosomes and a radiolabeled aminoacyl-tRNA substrate. Binding inhibition is measured by filtration. Vasopressin receptor binding assays use renal membranes and a radiolabeled vasopressin analog. |
| Cell Assay |
Methodology for HPLC Analysis of Demeclocycline Calcium: The concentration of demeclocycline calcium in pharmaceutical formulations or experimental mixtures is determined using validated high-performance liquid chromatography (HPLC) methods . Samples are extracted using 0.1 mol/L HCl. The extract is analyzed via HPLC utilizing an octadecylsilyl (C18) column with UV detection at 267 nm. The mobile phase consists of a mixture of disodium phosphate solution and dimethylformamide (DMF). Due to the calcium salt form, the method allows for the conversion of the calcium salt to the hydrochloride salt to enable successful validation and quantification . The standard curve is linear with a coefficient of determination (R²) of 0.9998 for demeclocycline hydrochloride, and method precision shows a standard deviation of 0.69% .
In vitro susceptibility testing uses standard microdilution methods per CLSI guidelines. Bacterial isolates are cultured in Mueller-Hinton broth, and demeclocycline is added at twofold dilutions. After 16-20 h at 35°C, MIC values are determined by visual inspection. |
| Animal Protocol |
While specific animal protocols for demeclocycline calcium are limited in the current search results, studies on the interaction of demeclocycline calcium with calcium hydroxide have been conducted using validated analytical methods . These studies typically involve mixing Ledermix® Paste (containing demeclocycline calcium) with calcium hydroxide in a 50:50 ratio by weight. The mixtures are incubated at 37°C for various time points (0, 1, 18, 24, 72 hours, and 7 days) to simulate clinical conditions. Following incubation, samples are extracted using 0.1 mol/L HCl and analyzed by HPLC to determine the remaining concentration of demeclocycline (converted to the hydrochloride salt for quantification). Descriptive statistics are provided, and results are expressed as percentage loss compared to baseline .
In vivo, demeclocycline is tested in animal models of infection and SIADH. A typical protocol involves oral administration (10-100 mg/kg) in mice or rats. Bacterial clearance is assessed in infection models. Urine output and osmolality are measured in SIADH models. |
| ADME/Pharmacokinetics |
The pharmacokinetic properties of demeclocycline calcium are expected to be similar to those of demeclocycline hydrochloride after absorption, as the calcium salt dissociates in the gastrointestinal tract. Demeclocycline is absorbed more slowly than tetracycline, with a time to reach peak concentration (Tmax) of approximately 4 hours after oral administration . After a 150 mg oral dose, mean plasma concentrations are 0.46 mcg/mL at 1 hour and 1.22 mcg/mL at 3 hours . The serum elimination half-life (t₁/₂) ranges between 10 and 16 hours . Plasma protein binding is approximately 40% by dialysis equilibrium method and 90% by ultra-filtration method . The renal clearance rate is 35 mL/min/1.73 m², less than half that of tetracycline . Following a single 150 mg dose, 44% is excreted in urine within 96 hours . Food, dairy products, and antacids containing aluminum, calcium, or magnesium reduce absorption by more than 50% .
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| Toxicity/Toxicokinetics |
Demeclocycline calcium shares the toxicity profile of the tetracycline class. The most distinctive adverse effect is nephrogenic diabetes insipidus (polyuria, polydipsia, weakness), which is dose-dependent and reversible upon discontinuation . Photosensitivity manifested as an exaggerated sunburn reaction can occur, and treatment should be discontinued at the first sign of skin erythema . Tetracyclines can cause permanent tooth discoloration (yellow-gray-brown) and enamel hypoplasia when used during tooth development (last half of pregnancy, infancy, and childhood up to age 8 years) . They can also cause fetal harm when administered to pregnant women, including retardation of skeletal development . Other adverse effects include gastrointestinal disturbances (anorexia, nausea, vomiting, diarrhea), Clostridioides difficile-associated diarrhea, pseudotumor cerebri (benign intracranial hypertension), and increases in BUN (especially in patients with renal impairment) . The anti-anabolic action may cause an increase in BUN, and hepatotoxicity has been reported rarely .
|
| References |
| Molecular Formula |
C42H40CACL2N4O16
|
|---|---|
| Molecular Weight |
967.77
|
| Exact Mass |
966.144
|
| Elemental Analysis |
C, 52.13; H, 4.17; Ca, 4.14; Cl, 7.33; N, 5.79; O, 26.45
|
| CAS # |
17146-81-5
|
| Related CAS # |
127-33-3;64-73-3 (HCl);13215-10-6 (hydrate);17146-81-5 (calcium);
|
| PubChem CID |
72941516
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
2.826
|
| Hydrogen Bond Donor Count |
10
|
| Hydrogen Bond Acceptor Count |
18
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
65
|
| Complexity |
961
|
| Defined Atom Stereocenter Count |
10
|
| SMILES |
CN(C)[C@H]1[C@@H]2C[C@@H]3[C@@H](C4=C(C=CC(=C4C(=C3C(=O)[C@@]2(C(=C(C1=O)C(=O)N)O)O)[O-])O)Cl)O.CN(C)[C@H]1[C@@H]2C[C@@H]3[C@@H](C4=C(C=CC(=C4C(=C3C(=O)[C@@]2(C(=C(C1=O)C(=O)N)O)O)[O-])O)Cl)O.[Ca+2]
|
| InChi Key |
UXOZEKMTWNWUFI-IQDXIELBSA-L
|
| InChi Code |
InChI=1S/2C21H21ClN2O8.Ca/c2*1-24(2)14-7-5-6-10(16(27)12-9(25)4-3-8(22)11(12)15(6)26)18(29)21(7,32)19(30)13(17(14)28)20(23)31/h2*3-4,6-7,14-15,25-26,28-29,32H,5H2,1-2H3,(H2,23,31)/q+2/p-2/t2*6-,7-,14-,15-,21-/m00./s1
|
| Chemical Name |
calcium
(5S,5aS,6aS,7S,10aS)-9-carbamoyl-4-chloro-7-(dimethylamino)-5,8,10a,11-tetrahydroxy-10,12-dioxo-5,5a,6,6a,7,10,10a,12-octahydrotetracen-1-olate
|
| Synonyms |
Detravis; Ledermycin; Demeclocycline calcium; Calcium demethylchlortetracycline; UNII-SD6S4YY5HP; SD6S4YY5HP; 17146-81-5;Demeclocycline calcium
|
| 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)
|
| 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 | 1.0333 mL | 5.1665 mL | 10.3330 mL | |
| 5 mM | 0.2067 mL | 1.0333 mL | 2.0666 mL | |
| 10 mM | 0.1033 mL | 0.5167 mL | 1.0333 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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