| Size | Price | |
|---|---|---|
| 50mg | ||
| Other Sizes |
| Targets |
D1/2 receptor
Zuclopenthixol targets dopamine D1 and D2 receptors. It also binds to alpha1-adrenergic receptors and 5-HT2 receptors with high affinity, and to histamine H1 receptors with weaker affinity. Its antipsychotic effects are primarily mediated through D2 receptor antagonism, while its side-effect profile is influenced by its activity at other receptors. |
|---|---|
| ln Vitro |
Zuclopenthixol, also known as Zuclopentixol or Zuclopenthixolum, is an antipsychotic agent. Zuclopenthixol is a thioxanthene-based neuroleptic with therapeutic actions similar to the phenothiazine antipsychotics. It is an antagonist at D1 and D2 dopamine receptors. Major brands of zuclopenthixol are Cisordinol, Acuphase, and Clopixol. This drug is a liquid. This compound belongs to the thioxanthenes. These are organic polycyclic compounds containing a thioxanthene moiety, which is an aromatic tricycle derived from xanthene by replacing the oxygen atom with a sulfur atom. Known drug targets of zuclopenthixol include 5-hydroxytryptamine receptor 2A, D(1B) dopamine receptor, D(2) dopamine receptor, D(1A) dopamine receptor, and alpha-1A adrenergic receptor. It is known that zuclopenthixol is metabolized by Cytochrome P450 2D6. Zuclopenthixol was approved for use in Canada in 2011, but is not approved for use in the United States.
In vitro, Zuclopenthixol acts as a mixed dopamine D1/D2 receptor antagonist. Its receptor binding profile includes high affinity for alpha1-adrenergic and 5-HT2 receptors, weaker histamine H1 receptor blocking activity, and lower affinity for muscarinic cholinergic and alpha2-adrenergic receptors. |
| ln Vivo |
Animals treated with succinyleptidol (0.2 and 0.4 mg/kg) displayed a pharmacological behavioral profile that included decreased aggression but no locomotor activity. By contrast, the maximum dose (0.4 mg/kg) caused a considerable increase in immobility along with its anti-aggression effect. No resistance against aggressiveness or locomotor activity induced by Zuclopenthixol was seen during subchronic therapy [1]. Zuclopenthixol raised MDA levels considerably at doses of 0.7 and 1.4 mg/kg. The effects of the two dosing levels on brain reserve MDA levels, however, were identical. Animals receiving 1.4 mg/kg of Zuclopenthixol had much lower GSH levels. However, the drug's reduced dosage had no discernible effect. The GSH levels of animals treated with 0.7 or 1.4 mg/kg Zuclopenthixol were considerably greater than those of those treated with SCO. When compared to animals treated natively, the administration of 0.7 mg/kg Zuclopenthixol markedly improved GSHPx activity [2].
In vivo, Zuclopenthixol is used as an antipsychotic agent for the treatment of schizophrenia and other psychotic disorders. Its therapeutic effects are mediated through dopamine D2 receptor antagonism, while its side effects are related to its activity at other receptor targets. |
| Enzyme Assay |
In vitro receptor binding assays for Zuclopenthixol are performed using membrane preparations expressing dopamine D1 and D2 receptors, as well as other receptors (alpha1-adrenergic, 5-HT2, histamine H1, muscarinic cholinergic, and alpha2-adrenergic receptors). Radioligand competition binding assays are used to measure the compound's affinity for these receptors, and Ki or IC50 values are calculated from competition curves.
|
| Cell Assay |
In vitro cellular assays for Zuclopenthixol are performed using cells expressing dopamine receptors or other target receptors. Cells are treated with the compound, and receptor-mediated signaling pathways (e.g., cAMP accumulation for D1 receptors or calcium mobilization for D2 receptors) are measured. The compound's antagonist activity is quantified by its ability to inhibit agonist-induced signaling.
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| Animal Protocol |
In vivo animal experiments for Zuclopenthixol are typically conducted in rodent models of psychosis or behavioral assays. The compound is administered via oral or intraperitoneal routes, and its antipsychotic-like effects are assessed using behavioral tests such as the prepulse inhibition (PPI) test or conditioned avoidance response (CAR) test. Side effects such as catalepsy are also evaluated.
|
| ADME/Pharmacokinetics |
Absorption
After entering body fluids, the decanoate ester is slowly released from the reservoir and subsequently hydrolyzed to the active ingredient, zoclothiasol. Since zoclothiasol itself is a short-acting drug, the decanoate ester provides sustained-release. Excretion Route Primarily excreted in feces, with approximately 10% excreted in urine. Volume of Distribution 20 L/kg. Clearance Approximately 0.9 L/min. Metabolism/Metabolites Zoclothiasol is primarily metabolized via sulfoxide oxidation, side-chain N-dealkylation, and glucuronic acid conjugation. The metabolites have no pharmacological activity. Biological Half-Life Tablets: 20 hours (range 12-28 hours); sustained-release formulation: 19 days. The pharmacokinetic properties of Zuclopenthixol have been characterized in preclinical and clinical studies. The dihydrochloride salt has a molecular weight of 473.89, molecular formula C22H27Cl3N2OS. The compound is a thioxanthene derivative with a typical antipsychotic profile. Further PK details, including half-life and bioavailability, are available from the manufacturer's data sheets. |
| Toxicity/Toxicokinetics |
Use during pregnancy and lactation
◉ Overview of use during lactation Zoclothiasol has not yet received marketing approval from the U.S. Food and Drug Administration (FDA), but it is available in other countries. Limited information suggests that low concentrations of the drug in breast milk are observed with mothers taking oral doses not exceeding 50 mg daily or 72 mg extended-release injections every two weeks, and no short-term adverse effects have been observed in breastfed infants. Long-term data are currently unavailable. One international guideline recommends that women taking zoclothiasol should not breastfeed. However, a safety rating system suggests that cautious use of zoclothiasol during lactation is feasible. Infants should be closely monitored when using zoclothiasol during lactation until more data become available. ◉ Effects on breastfed infants Six women received zoclothiasol treatment during lactation. Five women took 4 to 50 mg orally daily, and one woman received a 72 mg extended-release injection every two weeks. The breastfed infants ranged in age from 3 days to 10 months, with 5 infants being 2 months or younger. No immediate adverse reactions such as infant lethargy were observed. ◉ Effects on breastfeeding and breast milk As of the revision date, no relevant published information was found. Drug and Lactation Database (LactMed) Protein binding rate: 98-99% The toxicity profile of Zuclopenthixol is well established from its clinical use as an antipsychotic. Common adverse effects include extrapyramidal symptoms, sedation, and anticholinergic effects. The compound's safety profile is influenced by its activity at dopamine, adrenergic, serotonin, and histamine receptors. |
| References |
[1]. Khalifa AE, et al. Pro-oxidant activity of zuclopenthixol in vivo: differential effect of the drug on brain oxidative status of scopolamine-treated rats. Hum Exp Toxicol. 2004 Aug;23(9):439-45.
[2]. Manzaneque JM, et al. An ethopharmacological assessment of the effects of zuclopenthixol on agonistic interactions in male mice. Methods Find Exp Clin Pharmacol. 1999 Jan-Feb;21(1):11-5. [3]. Bryan EJ, et al. Zuclopenthixol dihydrochloride for schizophrenia. Cochrane Database Syst Rev. 2017 Nov 16;11(11):CD005474. |
| Additional Infomation |
See also: Zuclopenthixol (Note moved to).
Zuclopenthixol dihydrochloride is also known as (Z)-Clopenthixol dihydrochloride. It is a thioxanthene-based neuroleptic with therapeutic actions similar to the phenothiazine antipsychotics. The compound is a mixed dopamine D1/D2 receptor antagonist. This product is for research use only. |
| Molecular Formula |
C22H25N2OSCL.2[HCL]
|
|---|---|
| Molecular Weight |
473.88658
|
| Exact Mass |
472.09096
|
| Elemental Analysis |
C, 55.76; H, 5.74; Cl, 22.44; N, 5.91; O, 3.38; S, 6.77
|
| CAS # |
58045-23-1
|
| Related CAS # |
Zuclopenthixol;53772-83-1; trans-Clopenthixol dihydrochloride;58045-22-0;Zuclopenthixol-d4 succinate;1246833-97-5;Zuclopenthixol dihydrochloride;58045-23-1; 85721-05-7 (acetate); 53772-83-1; 58045-23-1 (HCl); 64053-00-5 (decanoate)
|
| PubChem CID |
6433208
|
| Appearance |
Light yellow to yellow solid powder
|
| Boiling Point |
577.4ºC at 760 mmHg
|
| Flash Point |
303ºC
|
| LogP |
4.914
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
29
|
| Complexity |
509
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1CN(CCN1CCC=C2C3=CC=CC=C3SC4=C2C=C(C=C4)Cl)CCO.Cl.Cl
|
| InChi Key |
LPWNZMIBFHMYMX-MHKBYHAFSA-N
|
| InChi Code |
InChI=1S/C22H25ClN2OS.2ClH/c23-17-7-8-22-20(16-17)18(19-4-1-2-6-21(19)27-22)5-3-9-24-10-12-25(13-11-24)14-15-26;;/h1-2,4-8,16,26H,3,9-15H2;2*1H/b18-5-;;
|
| Chemical Name |
2-[4-[(3Z)-3-(2-chlorothioxanthen-9-ylidene)propyl]piperazin-1-yl]ethanol;dihydrochloride
|
| Synonyms |
Zuclopenthixol dihydrochloride; 58045-23-1; Zuclopenthixol hydrochloride; Cisordinol; Clopenthixol cis(Z)-form dihydrochloride; Zuclopenthixol (dihydrochloride); DTXSID5045332; 7042692VYN;
|
| 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) |
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 | 2.1102 mL | 10.5510 mL | 21.1019 mL | |
| 5 mM | 0.4220 mL | 2.1102 mL | 4.2204 mL | |
| 10 mM | 0.2110 mL | 1.0551 mL | 2.1102 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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