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 may be erratic and peak plasma concentrations show large interindividual differences.
IV ADMIN RESULTS PEAK IN ABOUT 5 MIN, IM IN ABOUT 20-30 MIN, ORAL IN ABOUT 1-2 HR. PARENTERAL EFFECTS ARE MORE PREDICTABLE, & USUALLY REQUIRE ABOUT HALF ORAL DOSAGE FOR SOME COMPARABLE EFFECTS.

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Metabolism / Metabolites
Hepatic, primarily to N-desmethylpromazine and promazine sulfoxide.
YIELDS DEMETHYLPROMAZINE, PROMAZINE-N-OXIDE, & PROMAZINE SULFOXIDE IN MAN & IN RAT; YIELDS 3-HYDROXYPROMAZINE & PHENOTHIAZINE IN MAN. /FROM TABLE/
...METAB...BY OXIDATIVE PROCESSES MEDIATED LARGELY BY HEPATIC MICROSOMAL & OTHER DRUG-METABOLIZING ENZYMES. CONJUGATION WITH GLUCURONIC ACID...PROMINENT ROUTE.../PRC: REACTIONS INCL HYDROXYLATION, DEMETHYLATION, SULFOXIDE FORMATION; METABOLIC ALTERATIONS IN SIDE CHAIN MAY ALSO OCCUR/. /PHENOTHIAZINES/
Promazine has known human metabolites that include Promazine 5-sulfoxide and N-Desmethyl promazine.
Hepatic, primarily to N-desmethylpromazine and promazine sulfoxide. Absorption may be erratic and peak plasma concentrations show large interindividual differences. The metabolism occurs through oxidative processes mediated largely by hepatic microsomal and other drug metabolizing enzymes. Antoher step is the conjugaion with glucuronic acid. Other reactions include hydroxylation, demetylation, and sulfoxide formation. Moreover, metabolic alterations in side chain may also occur (A308, A631).

Toxicity Summary
Promazine 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. Promazine'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. Promazine 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 promazine.

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Protein Binding
94%

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Toxicity Data
LD50: 140 mg/kg (Intraperitoneal, Mouse)

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Interactions
RABBIT, RAT, & SHEEP TRIALS INDICATE IT MAY HELP REDUCE TOXIC EFFECTS OF CARBON TETRACHLORIDE. ... HAS INCR TOXICITY OF ORGANOPHOSPHORUS OR OTHER ACETYLCHOLINESTERASE INHIBITORS & PROCAINE.
...PHENOTHIAZINES...MAY PRODUCE ADDITIVE HYPOTENSIVE EFFECTS WITH PROPRANOLOL. /PHENOTHIAZINES/
...OTHER ANTIPSYCHOTIC DRUGS ... MAY BLOCK ANTIHYPERTENSIVE EFFECTS OF GUANETHIDINE ... /PHENOTHIAZINES/
Additive QT interval prolongation may increase the risk of ventricular tachycardia when /probucol is used with phenothiazines/. /Phenothiazines/
For more Interactions (Complete) data for PROMAZINE (31 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat oral 350 mg/kg
LD50 Rat sc 192 mg/kg
LD50 Rat iv 14,500 ug/kg
LD50 Mouse oral 401 mg/kg
For more Non-Human Toxicity Values (Complete) data for PROMAZINE (8 total), please visit the HSDB record 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 deriative in which the phenothiazine tricycle has a 3-(dimethylaminopropyl) group at the N-10 position. It has a role as a dopaminergic antagonist, a H1-receptor antagonist, a muscarinic antagonist, a serotonergic antagonist, a phenothiazine antipsychotic drug, an antiemetic and an EC 3.4.21.26 (prolyl oligopeptidase) inhibitor. It is a member of phenothiazines and a tertiary amine.
A phenothiazine with actions similar to chlorpromazine but with less antipsychotic activity. It is primarily used in short-term treatment of disturbed behavior and as an antiemetic. It is currently not approved for use in the United States.
Promazine is only found in individuals that have used or taken this drug. It is a phenothiazine with actions similar to chlorpromazine but with less antipsychotic activity. It is primarily used in short-term treatment of disturbed behavior and as an antiemetic. Promazine 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. Promazine'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. Promazine 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 promazine.
A phenothiazine with actions similar to CHLORPROMAZINE but with less antipsychotic activity. It is primarily used in short-term treatment of disturbed behavior and as an antiemetic.

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Drug Indication
Used as an adjunct for short term treatment of moderate and severe psychomotor agitation. Also used to treat agitation or restlessness in the elderly.

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Mechanism of Action
Promazine 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. Promazine'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. Promazine 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 promazine.
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; Antipsychotic Agents, Phenothiazine; Dopamine Antagonists
EFFECTIVE IN MGMNT OF MANIFESTATIONS OF PSYCHOTIC DISORDERS. IT IS PROBABLY EFFECTIVE FOR...RELIEF OF APPREHENSION PRIOR TO SURGERY, & FOR REDUCING AGITATION & TENSION, ASSOC WITH MILD ALCOHOL WITHDRAWAL UNDER SUPERVISION.
IT IS ALSO SIMILAR TO CHLORPROMAZINE IN ITS ACTIONS, BUT ITS POTENCY...LOWER.
MEDICATION (VET): EXTENSIVE, TO CONTROL INTRACTABLE ANIMALS, RELIEVE PAIN, CONTROL MOTION SICKNESS, FACILITATE HANDLING & EXAMINATION, POTENTIATE GENERAL ANESTHETICS, & ENHANCE BENEFITS OF LOCAL ANESTHETICS. USED TO MINIMIZE WT LOSS & CALM CATTLE DURING SHIPPING, AS SURGICAL AID, IN CALMING WILD OBSTETRICAL PT...
For more Therapeutic Uses (Complete) data for PROMAZINE (7 total), please visit the HSDB record page.

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Drug Warnings
PROMAZINE [SPARINE] IS OBSOLETE BECAUSE IT HAS EXTREMELY WEAK ANTIPSYCHOTIC ACTION & CAUSES GREATER INCIDENCE OF ADVERSE EFFECTS.
...PROMAZINE IS CONTRAINDICATED IN STUPOROUS OR PRECOMATOSE PT, AS WELL AS IN THOSE WITH CARDIAC OR CEREBROVASCULAR INSUFFICIENCY. ANTICHOLINERGIC-LIKE ACTIONS OF PROMAZINE MAY BE DETRIMENTAL IN PT WITH ANGLE-CLOSURE GLAUCOMA.
SINCE THESE AGENTS HAVE ANTIEMETIC PROPERTIES, THEY MAY MASK SIGNS OF DRUG OVERDOSAGE & OBSCURE SYMPTOMS OF BRAIN TUMOR OR INTESTINAL OBSTRUCTION. ... SHOULD ALSO BE USED WITH EXTREME CAUTION IN PT WITH CARDIOVASCULAR DISEASE, IMPAIRED LIVER FUNCTION, OR WITH HISTORY OF GASTRIC ULCER... /PHENOTHIAZINES/
ALTHOUGH SOME OF MORE SERIOUS TOXIC EFFECTS OF CHLORPROMAZINE HAVE NOT BEEN ENCOUNTERED WITH PROMAZINE, IT SHOULD BE USED WITH SAME DEGREE OF CAUTION.
For more Drug Warnings (Complete) data for PROMAZINE (25 total), please visit the HSDB record page.

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Pharmacodynamics
Promazine belongs to a group of medications known as the phenothiazine antipsychotics. It acts by blocking a variety of receptors in the brain, particularly dopamine receptors. Dopamine is involved in transmitting signals between brain cells. When there is an excess amount of dopamine in the brain it causes over-stimulation of dopamine receptors. These receptors normally act to modify behaviour and over-stimulation may result in psychotic illness. Promazine hydrochloride blocks these receptors and stops them becoming over-stimulated, thereby helping to control psychotic illness. Promazine has weak extrapyramidal and autonomic side effects which lead to its use in the elderly, for restless or psychotic patients. Its anti-psychotic effect is also weaker and it is not useful in general psychiatry.

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.)