Promazine's half-lives (KD) on the human norepinephrine, serotonin, and dopamine transporters are 25, 190, and 8400 nM, respectively [3].

Absorption, Distribution and Excretion
Absorption can be unstable, and peak plasma concentrations vary considerably among individuals. Peak concentrations are reached approximately 5 minutes after intravenous administration, 20-30 minutes after intramuscular administration, and 1-2 hours after oral administration. Parenteral administration is more predictable, typically requiring only half the oral dose to achieve similar effects. Metabolism/Metabolites Metabolized primarily in the liver, producing N-demethylPromazine and Promazine sulfoxides. In humans and rats, demethylPromazine, Promazine-N-oxide, and Promazine sulfoxides are produced; in humans, 3-hydroxyPromazine and phenothiazine are produced. /Excerpt from Table/ ...Metabolism... Primarily metabolized via hepatic microsomes and other drug-metabolizing enzymes-mediated oxidation. Glucuronide binding...Main pathway.../PRC: Reactions include hydroxylation, demethylation, sulfoxide formation; metabolic alterations of side chains may also occur/. /Phenothiazines/
The known metabolites of Promazine include Promazine-5-sulfoxide and N-demethylPromazine.
It is primarily metabolized in the liver to N-demethylPromazine and Promazine sulfoxide. Absorption can be unstable, and peak plasma concentrations vary considerably among individuals. The metabolism of this drug mainly occurs through oxidation processes, primarily mediated by hepatic microsomes and other drug-metabolizing enzymes. Another step is conjugation with glucuronide. Other reactions include hydroxylation, demethylation, and sulfoxide formation. Furthermore, metabolic alterations may also occur in the side chains (A308, A631).

Toxicity Summary
Promazine is an antagonist of dopamine receptors types 1, 2, and 4, 5-HT receptors types 2A and 2C, muscarinic receptors types 1 through 5, α1 receptors, and histamine H1 receptors. Promazine's antipsychotic effect stems from its antagonistic activity against dopamine and serotonin type 2 receptors, with higher activity against serotonin type 2 receptors than against dopamine type 2 receptors. This may explain its lack of extrapyramidal side effects. Promazine does not appear to block dopamine within the tuberous-infundibular bundle, therefore its incidence of hyperprolactinemia is lower than with typical antipsychotics or risperidone. Promazine also has antagonistic effects against muscarinic receptors, H1 receptors, and α1 receptors.

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Protein binding rate
94%Toxicity data
LD50: 140 mg/kg (intraperitoneal injection, mice)Interactions
Rabbit, rat, and sheep studies suggest that Promazine may help mitigate the toxic effects of carbon tetrachloride. …Increases the toxicity of organophosphates or other acetylcholinesterase inhibitors and procaine.
…Phenothiazines…May produce an additive hypotensive effect when used in combination with propranolol.
Phenothiazines… …Other antipsychotics…May block the hypotensive effect of guanethidine…Phenothiazines… When probucol is used in combination with phenothiazines, QT interval prolongation may increase the risk of ventricular tachycardia. /Phenothiazines/
For more complete data on interactions of Promazine (31 in total), please visit the HSDB record page.

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Non-human toxicity values
Oral LD50 in rats: 350 mg/kg
Subcutaneous LD50 in rats: 192 mg/kg
Intravenous LD50 in rats: 14,500 ug/kg
Oral LD50 in mice: 401 mg/kg
For more complete non-human toxicity data for Promazine (8 in total), please visit the HSDB records page.

[1]. Gareri P, et al. Conventional and atypical antipsychotics in the elderly : a review. Clin Drug Investig. 2003;23(5):287-322.
[2]. Myers PR, et al. Characterization of a depolarizing dopamine response in a vertebrate neuronal somatic cell hybrid. J Cell Physiol. 1977;91(1):103-118.
[3]. Tatsumi M, et al. Pharmacological profile of neuroleptics at human monoamine transporters. Eur J Pharmacol. 1999;368(2-3):277-283.

Promazine is a phenothiazine derivative with a 3-(dimethylaminopropyl) group attached to the N-10 position of its phenothiazine tricyclic ring. It possesses various pharmacological activities, including dopaminergic antagonist, H1 receptor antagonist, muscarinic receptor antagonist, serotonergic antagonist, phenothiazine antipsychotic, antiemetic, and EC 3.4.21.26 (prolyl oligopeptidase) inhibitor. It belongs to the phenothiazine class of compounds and is also a tertiary amine. Promazine's effects are similar to chlorpromazine, but its antipsychotic activity is weaker. It is mainly used for short-term treatment of behavioral disorders and as an antiemetic. Currently, it has not been approved in the United States. Promazine is only present in individuals who have previously used or taken this drug. Promazine is a phenothiazine drug with a mechanism of action similar to chlorpromazine, but its antipsychotic activity is weaker. It is mainly used for short-term treatment of behavioral disorders and as an antiemetic. Promazine is an antagonist of dopamine receptors types 1, 2, and 4, 5-HT receptors types 2A and 2C, muscarinic receptors types 1 through 5, α1 receptors, and histamine H1 receptors. Promazine's antipsychotic effect stems from its antagonistic effect on dopamine and 5-HT2 receptors, with higher activity against 5-HT2 receptors than against dopamine type 2 receptors. This may explain its lack of extrapyramidal side effects. Promazine does not appear to block dopamine within the tuberous-infundibular tract, thus its incidence of hyperprolactinemia is lower than with typical antipsychotics or risperidone. Promazine also has antagonistic effects on muscarinic receptors, H1 receptors, and α1 receptors. Promazine is a phenothiazine drug with similar effects to chlorpromazine, but with weaker antipsychotic activity. It is primarily used for short-term treatment of behavioral disorders and as an antiemetic. Drug Indications: For short-term adjunctive treatment of moderate to severe psychomotor agitation. It is also used to treat agitation or restlessness in the elderly.

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Mechanism of Action
Promazine is an antagonist of dopamine receptors types 1, 2, and 4, 5-HT2A and 2C receptors, muscarinic receptors types 1 to 5, α1 receptors, and histamine H1 receptors. Promazine's antipsychotic effect stems from its antagonistic effect on dopamine and serotonin type 2 receptors, with higher activity against serotonin 5-HT2 receptors than against dopamine type 2 receptors. This may explain its lack of extrapyramidal side effects. Promazine does not appear to block dopamine within the tuberous-infundibular bundle, which explains its lower incidence of hyperprolactinemia compared to typical antipsychotics or risperidone. Promazine also antagonizes muscarinic receptors, H1 receptors, and α1 receptors.
An adenylate cyclase exists in the limbic system and caudate nucleus, which can be specifically activated by dopamine. …Activation of this enzyme…can be blocked by…phenothiazine drugs. The therapeutic effects and side effects may be related to the inhibition of dopamine-activated adenylate cyclase. /Phenothiazines/
...Phenothiazines block dopamine receptors, increasing dopamine turnover in the striatum. This increased turnover is thought to be a result of neuronal feedback mechanisms. ...The firing activity of identified dopaminergic neurons in the substantia nigra and ventral tegmentum is increased by the antipsychotic phenothiazines. /Phenothiazines/

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Therapeutic Uses
Antiemetic; antipsychotic, phenothiazines; dopamine antagonists
Effectively controls the manifestations of mental disorders. It may be effective in relieving preoperative anxiety, reducing agitation and tension, and assisting in supervised mild alcohol withdrawal.
Its mechanism of action is similar to chlorpromazine, but with lower potency.
(Veterinary) Widely used for controlling unruly animals, relieving pain, controlling motion sickness, facilitating operation and examination, enhancing the effects of general anesthetics, and improving the efficacy of local anesthetics. Used to reduce weight loss during transport and to soothe cattle, as an adjunct to surgery, and to calm restless mothers in labor…
For more complete data on the therapeutic uses of Promazine (7 types), please visit the HSDB records page.

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Drug Warnings
Promazine [sparing] is obsolete because it has very weak antipsychotic effects and a higher incidence of adverse reactions.
…Promazine is contraindicated in patients in a coma or pre-coma state, and in patients with heart or cerebrovascular insufficiency.The anticholinergic-like effects of Promazine may be harmful to patients with angle-closure glaucoma.
Because these drugs have antiemetic effects, they may mask signs of overdose and symptoms of brain tumors or intestinal obstruction.…Extreme caution should be exercised in patients with cardiovascular disease, impaired liver function, or a history of peptic ulcers…/Phenothiazines/
Although Promazine has not been associated with some of the more serious toxicities of chlorpromazine, it should still be used with caution. For more complete data on drug warnings for Promazine (25 in total), please visit the HSDB records page.

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Pharmacodynamics
Promazine belongs to the phenothiazine class of antipsychotics. It works by blocking multiple receptors in the brain, particularly dopamine receptors. Dopamine is involved in signal transmission between brain cells. When there is an excess of dopamine in the brain, it leads to over-excitation of dopamine receptors. These receptors normally regulate behavior, and over-excitation can lead to psychosis. Promazine hydrochloride helps control psychosis by blocking these receptors, preventing their over-excitation. Promazine has milder extrapyramidal and autonomic nervous system side effects, therefore it is mainly used for the elderly, agitated patients, or those with psychosis. Its antipsychotic effect is also relatively weak and it is not suitable for the general treatment of psychosis.

C17H20N2S

284.42

284.135

58-40-2

Promazine hydrochloride;53-60-1

4926

Oily liq

1.133g/cm3

412.7ºC at 760mmHg

25°C

203.4ºC

1.6000 (estimate)

4.306

0

3

4

20

285

0

CN(C)CCCN1C2=CC=CC=C2SC3=CC=CC=C31

ZGUGWUXLJSTTMA-UHFFFAOYSA-N

InChI=1S/C17H20N2S/c1-18(2)12-7-13-19-14-8-3-5-10-16(14)20-17-11-6-4-9-15(17)19/h3-6,8-11H,7,12-13H2,1-2H3

N,N-dimethyl-3-phenothiazin-10-ylpropan-1-amine

Promazine NSC 31447 TomilEsparin SparineSinophenin

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)

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

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.)