Cis(Z)-flupentixol dihydrochloride is a potent and selective antagonist of dopamine DA D1/D2 receptors, with Ki values of 0.38 nM and 7 nM for D2 receptors and 5-HT2A, respectively. .

Physicochemical Properties

Molecular Formula	C23H27CL2F3N2OS
Molecular Weight	507.44
Exact Mass	506.117
Elemental Analysis	C, 54.44; H, 5.36; Cl, 13.97; F, 11.23; N, 5.52; O, 3.15; S, 6.32
CAS #	51529-01-2
Related CAS #	Flupentixol dihydrochloride;2413-38-9;Flupentixol;2709-56-0
PubChem CID	5282483
Appearance	Typically exists as solid at room temperature
Boiling Point	554.7ºC at 760 mmHg
Melting Point	194-202ºC
Flash Point	289.3ºC
LogP	6.081
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	5
Heavy Atom Count	32
Complexity	592
Defined Atom Stereocenter Count	0
SMILES	Cl[H].Cl[H].S1C2=C([H])C([H])=C([H])C([H])=C2/C(/C2C([H])=C(C(F)(F)F)C([H])=C([H])C1=2)=C(/[H])\C([H])([H])C([H])([H])N1C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])O[H])C([H])([H])C1([H])[H]
InChi Key	ZQAWQVWCKYGMNE-CVIBNLPVSA-N
InChi Code	InChI=1S/C23H25F3N2OS.ClH/c24-23(25,26)17-7-8-22-20(16-17)18(19-4-1-2-6-21(19)30-22)5-3-9-27-10-12-28(13-11-27)14-15-29;/h1-2,4-8,16,29H,3,9-15H2;1H/b18-5-;
Chemical Name	2-[4-[(3Z)-3-[2-(trifluoromethyl)thioxanthen-9-ylidene]propyl]piperazin-1-yl]ethanol;hydrochloride
Synonyms	Flupenthixol dihydrochloride; 2413-38-9; Emergil; cis-(Z)-Flupenthixol dihydrochloride; FLUPENTIXOL DIHYDROCHLORIDE; Fupentixol dihydrochloride; Flupentixol HCl; .
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)

Biological Activity

Targets	D2 Receptor (Ki = 0.38 nM); 5-HT2A Receptor (Ki = 7 nM)
ln Vitro	Of the 31 antipsychotics examined, the older traditional antipsychotics such as trifluperazine, pimozide, chlorpromazine, fluphenazine, haloperidol, and flupenthixol bind more tightly than dopamine itself to the dopamine D2 receptor, with dissociation constants that are lower than that for dopamine. The newer, atypical antipsychotics such as quetiapine, remoxipride, clozapine, olanzapine, sertindole, ziprasidone, and amisulpride all bind more loosely than dopamine to the dopamine D2 receptor and have dissociation constants higher than that for dopamine. These tight and loose binding data agree with the rates of antipsychotic dissociation from the human-cloned D2 receptor. For instance, radioactive haloperidol, chlorpromazine, and raclopride all dissociate very slowly over a 30-minute time span, while radioactive quetiapine, clozapine, remoxipride, and amisulpride dissociate rapidly, in less than 60 seconds. These data also match clinical brain-imaging findings that show haloperidol remaining constantly bound to D2 in humans undergoing 2 positron emission tomography (PET) scans 24 hours apart. Conversely, the occupation of D2 by clozapine or quetiapine has mostly disappeared after 24 hours.[2]
ln Vivo	Pretreatment with cis-(Z)-Flupentixol (0.25 or 0.5 mg/kg, i.p.) dose-dependently inhibits cocaine-induced activity [1].
Animal Protocol	Animal/Disease Models: Rat[1]. Doses: 0.125, 0.25 or 0.5 mg/kg. Management: Intellectual Property Experimental Results: Cocaine-induced reduction in activity.
Toxicity/Toxicokinetics	Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Flupenthixol is not approved for marketing in the United States by the U.S. Food and Drug Administration, but is available in other countries. Limited information indicates that maternal oral doses of up to 4 mg daily or depot injections of 40 mg every 2 weeks produced low levels in milk and breastfed infants' serum, and caused no adverse developmental consequences. A safety scoring system finds flupenthixol possible to use cautiously during breastfeeding. Until more data are available, flupenthixol should be used with careful infant monitoring during breastfeeding. ◉ Effects in Breastfed Infants A woman took flupenthixol 1 mg and nortriptyline 100 mg daily during pregnancy and flupenthixol 4 mg and nortriptyline 125 mg daily immediately postpartum. She exclusively breastfed her infant. Over a 4-month period, the infant showed no signs of adverse drug effects and had normal motor development with a maternal dosage of flupenthixol 2 mg daily and nortriptyline 75 mg daily. ◉ Effects on Lactation and Breastmilk Flupenthixol can increase serum prolactin and has caused galactorrhea. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.
References	[1]. Jennifer M Wenzel, et al. The dopamine antagonist cis-flupenthixol blocks the expression of the conditioned positive but not the negative effects of cocaine in rats. Pharmacol Biochem Behav. 2013 Dec;114-115:90-6. [2]. Philip Seeman, et al. Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38.
Additional Infomation	Cis-flupenthixol dihydrochloride is the dihydrochloride salt of cis-flupenthixol. It has a role as a geroprotector. It contains a cis-flupenthixol(2+). A thioxanthene neuroleptic that, unlike CHLORPROMAZINE, is claimed to have CNS-activating properties. It is used in the treatment of psychoses although not in excited or manic patients. (From Martindale, The Extra Pharmacopoeia, 30th ed, p595)

Solubility Data

Solubility (In Vitro)

DMSO : ~62.5 mg/mL (~123.17 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.9707 mL	9.8534 mL	19.7068 mL
	5 mM	0.3941 mL	1.9707 mL	3.9414 mL
	10 mM	0.1971 mL	0.9853 mL	1.9707 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.