D1/2 receptor

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.

Animals treated with zucloperidol (0.2 and 0.4 mg/kg) showed behavioral pharmacology following acute treatment, which included decreased aggressive behavior but unaltered locomotor activity (0.2 mg/kg). By contrast, a notable rise in immobility coincided with the anti-challenge effect at the maximum dose (0.4 mg/kg). No resistance to zuclopentixol against aggressiveness or locomotor activity was seen following subchronic therapy [1]. When zuclopenthixol (0.7 and 1.4 mg/kg) was administered, MDA levels were considerably higher than when the corresponding controls were used. On the MDA levels in the rat brain, however, there was no distinction between the two dose levels' effects. The administration of 1.4 mg/kg zucloperidol significantly lowered GSH levels in animals when compared with vehicle treatment and zuclopentixol (0.7 mg/kg) therapy, according to post hoc pairwise comparisons of averages between groups (n=12) receiving different dose levels of the drug (P<0.001). Nevertheless, the drug's lesser dosages had no effect on the rats' brains GSH levels. 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 mice treated with a vehicle, the administration of 0.7 mg/kg Zuclopenthixol dramatically boosted GSHPx activity [2].

Zuclopenthixol is a thioxanthene derivative which acts as a mixed dopamine D1/D2 receptor antagonist. Although the antiaggressive action of neuroleptic drugs is well known, the effects of zuclopenthixol on agonistic interactions have not been explored and there are no studies comparing acute and subchronic effects of this compound on aggression in rodents. In this work, we examined the action of zuclopenthixol (0.025-0.4 mg/kg), administered acutely or subchronically for 10 days, on agonistic behavior elicited by isolation in male mice. Individually housed mice were exposed to anosmic "standard opponents" 30 min after the drug administration, and encounters were videotaped and evaluated using an ethologically based analysis. After acute treatment, zuclopenthixol (0.2 and 0.4 mg/kg)-treated animals exhibited ethopharmacological profiles characterized by a decrease in offensive behaviors without impairment of motor activity (0.2 mg/kg). In contrast, the antiaggressive action of the highest dose used (0.4 mg/kg) was accompanied by a marked increase of immobility. After subchronic treatment, no tolerance to zuclopenthixol antiaggressive or motor activity was observed. Overall, this behavioral profile is similar to that observed with other typical neuroleptics.[1]

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Several clinical studies implicated oxidative stress in the pathophysiology of both psychosis and dementia. As dementia is commonly associated with psychosis, antipsychotic medications are of importance in the pharmacotherapy of dementia particularly as a number of antipsychotics were reported to demonstrate neuronal pro-oxidant and/or antioxidant properties. Impairment of learning and memory, as the most characteristic manifestation of dementia, could be induced in experimental animals by acute administration of scopolamine (SCO) with a resultant elevation in brain oxidative status. This study investigated the potential pro-oxidant and/or antioxidant activity of the antipsychotic drug zuclopenthixol acetate, as its effect on brain oxidative status has yet to be evaluated. A 2 x 3 between-subjects factorial design was used to investigate the simultaneous and interactive effects of zuclopenthixol (0.7 and 1.4 mg/kg i.p.) and SCO on rat brain malondialdehyde, glutathione, glutathione peroxidase and superoxide dismutase levels/activities. Results revealed a significant pro-oxidant effect for both zuclopenthixol and SCO alone conditions. In addition, combined treatment of zuclopenthixol and SCO was found to be significantly different compared to either treatment conditions with regard to their effect on different brain oxidative stress indices. Such findings may have valuable implications in the pharmacotherapy of both psychosis and dementia.[2]

Absorption, Distribution and Excretion
Decanoate ester is slowly released from the reservoir after entering the body fluid phase, subsequently hydrolyzing to the active substance, zoclothiasol. Since zoclothiasol itself is a short-acting drug, decanoate ester provides sustained-release. It is primarily excreted in feces, with approximately 10% excreted in urine. 20 L/kg. Approximately 0.9 L/min. Metabolism/Metabolites Zoclothiasol is primarily metabolized via sulfoxide oxidation, side-chain N-dealkylation, and glucuronic acid conjugation. The metabolites are not pharmacologically active. Biological Half-Life Tablets have a half-life of 20 hours (range 12-28 hours), while sustained-release formulations have a half-life of 19 days.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Zoclonthiazol has not been approved for marketing by 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 no more than 50 mg orally 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 against breastfeeding in women taking zoclothiazol. However, a safety rating system suggests that cautious use of zoclothiazol during lactation is feasible. Infants should be closely monitored when using zoclothiazol during lactation until more data become available.
◉ Effects on Breastfed Infants
Six women received zoclothiazol treatment while breastfeeding. 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 aged 2 months or younger. No immediate adverse reactions such as infant lethargy were observed.
◉ Effects on lactation and breast milk
As of the revision date, no relevant published information was found.

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Protein binding rate
98-99%

[1]. 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.
[2]. 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

Chloropenthioxine is a thiol derivative with a chlorine substituent at the 2-position and an alkylene group at the 10-position; its double bond stereochemical structure is undefined. It is an H1 receptor antagonist, serotonergic antagonist, alpha-adrenergic antagonist, dopaminergic antagonist, and also a first-generation antipsychotic. It is an N-alkylpiperazine, belonging to the primary alcohol class, and is also a thiol class compound. Zuclopenthixol, also known as zuclopenthixol or zuclopenthixol, is an antipsychotic drug. Zuclopenthixol is a thiol-class neuroleptic, with therapeutic effects similar to phenothiazine antipsychotics. It is an antagonist of D1 and D2 dopamine receptors. Major brands of zuclopenthixol include Cisordinol, Acuphase, and Clopixol. This drug is available in liquid form. Zuclopenthixol belongs to the thiol class of compounds. Thioxonides are organic polycyclic compounds containing a thioxonyl group, an aromatic tricyclic compound derived from thioxonol, in which the oxygen atom is replaced by a sulfur atom. Known drug targets of zoclopidogrel include serotonin receptor 2A, D(1B) dopamine receptor, D(2) dopamine receptor, D(1A) dopamine receptor, and α-1A adrenergic receptor. Zoclopidogrel is known to be metabolized by cytochrome P450 2D6. Zoclopidogrel was approved for marketing in Canada in 2011 but has not yet been approved for marketing in the United States.
Clopisoxane is a thioxonide compound with therapeutic effects similar to phenothiazine antipsychotics. It is an antagonist of D1 and D2 dopamine receptors.
A thioxonide drug with therapeutic effects similar to phenothiazine antipsychotics. It is an antagonist of D1 and D2 dopamine receptors. Drug Indications For the treatment of acute psychosis, such as mania or schizophrenia. However, because there are not sufficient and well-documented clinical trials of Zuclopenthixol acetate for psychiatric emergencies, caution should be exercised when using Zuclopenthixol acetate as an alternative to standard treatment (such as haloperidol, clothiapine, etc.). Zuclopenthixol acetate is not suitable for long-term use. FDA Label Mechanism of Action Zuclopenthixol is a typical thioxanthidine antipsychotic neuroblocker. It primarily works by antagonizing D1 and D2 dopamine receptors. Zuclopenthixol also has high affinity for α1-adrenergic and 5-HT2 receptors. It has weaker blocking activity against histamine H1 receptors and even lower affinity for muscarinic cholinergic and α2-adrenergic receptors.

C22H25CLN2OS

400.965

400.138

C, 65.90; H, 6.28; Cl, 8.84; N, 6.99; O, 3.99; S, 8.00

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)

5311507

Typically exists as solid at room temperature

1.289g/cm3

577.4ºC at 760mmHg

56-60ºC

303ºC

1.675

4.112

1

4

5

27

509

0

OCCN1CCN(CC/C=C2C3=C(SC4=C\2C=CC=C4)C=CC(Cl)=C3)CC1

WFPIAZLQTJBIFN-DVZOWYKESA-N

InChI=1S/C22H25ClN2OS/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/b18-5-

2-[4-[(3Z)-3-(2-chlorothioxanthen-9-ylidene)propyl]piperazin-1-yl]ethanol

Zuclopenthixol; 53772-83-1; Clopixol; Zuclopentixol; CLOPENTHIXOL; Zuclopentixol [Spanish]; Zuclopenthixolum [Latin]; Cisordinol;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~200 mg/mL (~498.80 mM)

Solubility in Formulation 1: 2.86 mg/mL (7.13 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 28.6 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.

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Solubility in Formulation 2: 2.86 mg/mL (7.13 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 28.6 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.

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 (Please use freshly prepared in vivo formulations for optimal results.)