Antibiotic action (vancomycin) is enhanced by thiethylperazine at as little as 2 μg/mL. With MIC values of 8 μg/mL and 16 μg/mL, respectively, Thietylperazine can inhibit isolates of vancomycin-susceptible Enterococcus faecalis ATCC 29212, vancomycin-resistant Enterococcus faecalis ATCC 51299, and vancomycin-resistant Enterococcus faecalis (VREF). mL and 8 μg/mL [3].

In young APP/PS1 mice, thiethylperazine (3 mg/kg; intramuscular injection; twice daily; for 30 days) dramatically decreased Aβ42 levels [2].

Animal/Disease Models: juvenile Aβ precursor protein (APPswe) and mutant presenilin-1 (PS1) (APP/PS1) mice [2]
Doses: 3 mg/kg
Route of Administration: intramuscularinjection; twice (two times) daily; for 30 Day
Experimental Results: Aβ42 levels were Dramatically diminished in APP/PS1 mice.

Absorption, Distribution and Excretion
Thiethylperazine is eliminated in the urine.
APPROX HALF OF METABOLITES OF COMMONLY USED PHENOTHIAZINES ARE FOUND IN URINE & REST IN FECES. 6 MO AFTER DISCONTINUATION OF THESE DRUGS, VARIOUS METABOLITES ARE DETECTABLE IN URINE. /PHENOTHIAZINES/
PHENOTHIAZINE TRANQUILIZERS CROSS PLACENTA RAPIDLY, & THEY HAVE BEEN MEASURED FOR MANY YR IN URINE & TISSUES OF NEONATES OF TREATED MOTHERS, BUT VERY LOW BLOOD LEVELS OF MOTHERS & FETUSES HAVE BEEN MEASURED ONLY RECENTLY... /PHENOTHIAZINES/

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Metabolism / Metabolites
IN PRINCIPLE, METABOLITES OF THIETHYLPERAZINE SIMILAR TO THOSE OF THIORIDAZINE SEEM TO BE FORMED. A LARGE PROPORTION OF THE DOSE IS SECRETED INTO BILE AS GLUCURONIDES.
... METAB ... ARE OXIDATIVE PROCESSES MEDIATED LARGELY BY GENETICALLY CONTROLLED HEPATIC MICROSOMAL OXIDASES & CONJUGATION PROCESSES. /PHENOTHIAZINES/

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Based on minimal excretion of other phenothiazine derivatives, it appears that occasional short-term use of thiethylperazine for the treatment of nausea and vomiting poses little risk to the breastfed infant.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Phenothiazines cause galactorrhea in 26 to 40% of female patients. Hyperprolactinemia appears to be the cause of the galactorrhea. The hyperprolactinemia is caused by the drug's dopamine-blocking action in the tuberoinfundibular pathway.

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Protein Binding
60%

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Interactions
/INTERACTS WITH/...GUANETHIDINE (BLOCKADE OF ANTIHYPERTENSIVE EFFECT); MORPHINE (POTENTIATES SEDATION); MEPERIDINE (INCR RESP DEPRESSION); BARBITURATES & OTHER CNS DEPRESSANTS INCL ALCOHOL (POTENTIATION RESULTING IN INCR SEDATIVE EFFECT OR PROLONGED POST-ANESTHETIC SLEEP TIME)... /MALATE & MALEATE/
/INTERACTS WITH/...LEVODOPA (DECR UPTAKE & EFFECTIVENESS); ANTICONVULSANTS (LOWERS SEIZURE THRESHOLD); PROCARBAZINE (POTENTIATION OF BEHAVIORAL ABNORMALITIES). /MALATE & MALEATE/

[1]. Case-control study of teratogenic potential of thiethylperazine, an anti-emetic drug. BJOG. 2003 May;110(5):497-9.

[2]. Cerebral amyloid-β proteostasis is regulated by the membrane transport protein ABCC1 in mice. J Clin Invest. 2011 Oct;121(10):3924-31.

[3]. Enhancement of vancomycin activity by phenothiazines against vancomycin-resistant Enterococcus faecium in vitro. Basic Clin Pharmacol Toxicol. 2010 Aug;107(2):676-9.

Thiethylperazine is a member of the class of phenothiazines that is perazine substituted by a ethylsulfanyl group at position 2. It has a role as a phenothiazine antipsychotic drug, a histamine antagonist, a muscarinic antagonist, a serotonergic antagonist, a dopaminergic antagonist and an antiemetic. It is a member of phenothiazines and a N-methylpiperazine. It is functionally related to a perazine.
A dopamine antagonist that is particularly useful in treating the nausea and vomiting associated with anesthesia, mildly emetic cancer chemotherapy agents, radiation therapy, and toxins. This piperazine phenothiazine does not prevent vertigo or motion sickness. (From AMA Drug Evaluations Annual, 1994, p457)
Thiethylperazine is a piperazine phenothiazine derivative and a dopamine antagonist used as antiemetic. Thiethylperazine blocks postsynaptic dopamine 2 (D2) receptors in the medullary chemoreceptor trigger zone (CTZ), thereby decreasing stimulation of the vomiting center in the brain. Peripherally, thiethylperazine blocks the vagus nerve in the gastrointestinal tract. In addition, this agent also shows antagonistic activities mediated through muscarinic receptors, H1-receptors, and alpha(1)-receptors.
A dopamine antagonist that is particularly useful in treating the nausea and vomiting associated with anesthesia, mildly emetic cancer chemotherapy agents, radiation therapy, and toxins. This piperazine phenothiazine does not prevent vertigo or motion sickness. (From AMA Drug Evaluations Annual, 1994, p457)

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Drug Indication
For the treatment or relief of nausea and vomiting.

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Mechanism of Action
Thiethylperazine is an antagonist at types 1, 2, and 4 dopamine receptors, 5-HT receptor types 2A and 2C, muscarinic receptors 1 through 5, alpha(1)-receptors, and histamine H1-receptors. Thiethylperazine's antipsychotic effect is due to antagonism at dopamine and serotonin type 2 receptors, with greater activity at serotonin 5-HT2 receptors than at dopamine type-2 receptors. This may explain the lack of extrapyramidal effects. Thiethylperazine does not appear to block dopamine within the tubero-infundibular tract, explaining the lower incidence of hyperprolactinemia than with typical antipsychotic agents or risperidone. Antagonism at muscarinic receptors, H1-receptors, and alpha(1)-receptors also occurs with thiethylperazine.
THERE IS AN ADENYLATE CYCLASE IN LIMBIC SYSTEM, AS WELL AS IN CAUDATE NUCLEUS, THAT IS SPECIFICALLY ACTIVATED BY DOPAMINE. ...ACTIVATION OF...ENZYME IS... BLOCKED BY...PHENOTHIAZINES. ...THERAPEUTIC EFFICACY & SIDE EFFECTS MAY RELATE TO INHIBITION OF DOPAMINE ACTIVATION OF ADENYLATE CYCLASE. /PHENOTHIAZINES/
...PHENOTHIAZINES, BLOCK DOPAMINE RECEPTORS & INCR TURNOVER RATE OF DOPAMINE IN CORPUS STRIATUM. INCR TURNOVER RATE IS BELIEVED TO BE RESULT OF NEURONAL FEEDBACK MECHANISM. ...FIRING OF.../IDENTIFIED DOPAMINERGIC NEURONS IN SUBSTANTIA NIGRA & VENTRAL TEGMENTAL AREAS/ IS INCR BY ANTIPSYCHOTIC PHENOTHIAZINES. /PHENOTHIAZINES/

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Therapeutic Uses
Antiemetics; Dopamine Antagonists
EXPTL USE (VET): THE EFFECT OF THIETHYLPERAZINE ON VESTIBULAR NYSTAGMUS IN RABBITS WAS INVESTIGATED. THE NYSTAGMUS WAS PROVOKED BY MEANS OF A TORSION SWING. A CLEAR SUPPRESSIVE EFFECT BUT LESS STRONG & SHORTER THAN CINNARIZINE & SULPIRIDE WAS SEEN WITH THIETHYLPERAZINE.
EXPTL USE (VET): DOGS FED 0.4 KG DOG FOOD WERE THEN INJECTED WITH 0.86 MG/KG THIETHYLPERAZINE IM & IRRADIATED BY (60)CO TELETHERAPY UNIT. THE DOSE OF RADIATION CAUSING EMESIS IN 50% (ED50) OF CONTROL DOGS WAS 170 RAD. ED50 WAS INCR TO 320 RAD BY THIETHYLPERAZINE.
A PHENOTHIAZINE ANTIEMETIC EFFECTIVE IN RELIEF OF NAUSEA & VOMITING FROM VARIOUS CAUSES. IT IS ALSO POSSIBLY EFFECTIVE FOR MGMNT OF VERTIGO. /MALEATE/
For more Therapeutic Uses (Complete) data for ETHYLTHIOPERAZINE (12 total), please visit the HSDB record page.

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Drug Warnings
IT SHOULD NOT BE USED IN PREGNANCY OR CHILDREN UNDER 12 YEARS OF AGE. OTHER CONTRAINDICATIONS & SIDE EFFECTS ARE THE SAME AS THOSE FOR OTHER PHENOTHIAZINES. /MALEATE/
THESE AGENTS SHOULD BE USED CAUTIOUSLY IN PT WITH SEVERE LIVER DISEASE & SEIZURE DISORDERS & IN ELDERLY PT. /ANTIEMETIC PHENOTHIAZINES/
... PHENOTHIAZINES ... SHOULD BE USED WITH EXTREME CAUTION, IF @ ALL, IN UNTREATED EPILEPTIC PT & IN PT UNDERGOING WITHDRAWAL FROM CENTRAL DEPRESSANT DRUGS SUCH AS ALCOHOL, BARBITURATES, AND BENZODIAZEPINES. PHENOTHIAZINES MAY BE USED IN EPILEPTICS IF MODERATE DOSES ARE ATTAINED GRADUALLY AND IF CONCOMITANT ANTICONVULSANT DRUG THERAPY IS MAINTAINED. /PHENOTHIAZINES/
...PRECAUTIONS SHOULD BE OBSERVED IN USE OF PHENOTHIAZINES FOR NAUSEA & VOMITING AS WITH USE OF POTENT ANALGESICS IN TREATMENT OF PAIN, BECAUSE THEY MAY MASK DIAGNOSTIC SYMPTOMS IN ACUTE SURGICAL CONDITIONS OR NEUROLOGICAL SYNDROMES. /PHENOTHIAZINES/
For more Drug Warnings (Complete) data for ETHYLTHIOPERAZINE (31 total), please visit the HSDB record page.

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Pharmacodynamics
Thiethylperazine, an atypical antipsychotic agent, is used to treat both negative and positive symptoms of schizophrenia, acute mania with bipolar disorder, agitation, and psychotic symptoms in dementia. Future uses may include the treatment of obsessive-compulsive disorder and severe behavioral disorders in autism. Structurally and pharmacologically similar to clozapine, Thiethylperazine binds to alpha(1), dopamine, histamine H1, muscarinic, and serotonin type 2 (5-HT2) receptors.

C22H29N3S2

399.615

399.18

1420-55-9

Thiethylperazine dimaleate;1179-69-7

5440

Light brown to gray solid powder

1.24g/cm3

559.8ºC at 760mmHg

62-64°

292.4ºC

1.5605 (estimate)

4.979

0

5

6

27

455

0

XCTYLCDETUVOIP-UHFFFAOYSA-N

InChI=1S/C22H29N3S2/c1-3-26-18-9-10-22-20(17-18)25(19-7-4-5-8-21(19)27-22)12-6-11-24-15-13-23(2)14-16-24/h4-5,7-10,17H,3,6,11-16H2,1-2H3

2-ethylsulfanyl-10-[3-(4-methylpiperazin-1-yl)propyl]phenothiazine

Norzine; Torecan; Thiethylperazine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

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

DMSO : ~100 mg/mL (~250.24 mM)

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.

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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).

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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)

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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).

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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

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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.

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