Promazine hydrochloride's half-life (KD) on the human norepinephrine, serotonin, and dopamine transporters is 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-demethylPromethazine and Promethazine sulfoxides. In humans and rats, demethylPromethazine, Promethazine-N-oxide, and Promethazine sulfoxides are produced; in humans, 3-hydroxyPromethazine 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 Promethazine include Promethazine-5-sulfoxide and N-demethylPromethazine.
It is primarily metabolized in the liver to N-demethylPromethazine and Promethazine 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).

Protein Binding
94%

[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.

Promethazine 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. Promethazine's effects are similar to chlorPromethazine, 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. Promethazine is only present in individuals who have previously used or taken this drug. Promethazine is a phenothiazine drug with a mechanism of action similar to chlorPromethazine, but its antipsychotic activity is weaker. It is mainly used for short-term treatment of behavioral disorders and as an antiemetic. Promethazine 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. Promethazine'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. Promethazine does not appear to block dopamine within the tuberous-infundibular tract, thus its incidence of hyperprolactinemia is lower than with typical antipsychotics or risperidone. Promethazine also has antagonistic effects on muscarinic receptors, H1 receptors, and α1 receptors. Promethazine is a phenothiazine drug with similar effects to chlorPromethazine, 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
Promethazine 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. Promethazine'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. Promethazine does not appear to block dopamine within the tuberous-infundibular bundle, which explains its lower incidence of hyperprolactinemia compared to typical antipsychotics or risperidone. Promethazine 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 neural feedback mechanisms. ...The firing activity of identified dopaminergic neurons in the substantia nigra and ventral tegmentum has been increased by the antipsychotic drug phenothiazines. /Phenothiazines/

C17H20N2S.HCL

320.88004

320.111

53-60-1

Promazine;58-40-2

4926

Oily liq

412.7ºC at 760mmHg

174-176ºC

203.4ºC

5.108

0

3

4

20

285

0

CN(C)CCCN1C2=C(C=CC=C2)SC3=CC=CC=C13.[H]Cl

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

2934.99.9001

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.

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

H2O : ~100 mg/mL (~311.64 mM)
DMSO : ~100 mg/mL (~311.64 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.79 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: ≥ 2.5 mg/mL (7.79 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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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Solubility in Formulation 3: ≥ 2.5 mg/mL (7.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 100 mg/mL (311.64 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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