Triprolidine (mature human dendritic cells) inhibits histamine H1 and lowers CD45 expression [1]

Triplidine (292.81-1467.20 μg/kg; intraperitoneal injection; male Sprague-Dawley rats) generates dose-dependent spinal motor and sensory inhibition in rats [2].

Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat (300-350 g) [2]
Doses: 292.81, 488.02, 733.60, 1098.83 and 1467.20 μg/kg
Route of Administration: Intrathecal injection
Experimental Results:Caused dose-dependent spinal cord block.

Absorption, Distribution and Excretion
Rapidly absorbed in the intestinal tract.
The H1 antagonists are well absorbed from the GI tract. Following oral administration, peak plasma concn are achieved in 2 to 3 hr and effects usually last 4 to 6 hr; however, some of the drugs are much longer acting ... . /Histamine Antagonists: H1 Antagonists/
... H1 antagonists are eliminated more rapidly by children than by adults and more slowly in those with severe liver disease. /Histamine Antagonists: H1 Antagonists/

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Metabolism / Metabolites
MAIN SITE OF METABOLIC TRANSFORMATION IS LIVER. /ANTIHISTAMINES/

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Biological Half-Life
4 to 6 hours.
Elimination: 3 to 3.3 hours

Hepatotoxicity
Like most first generation antihistamines, triprolidine has not been linked to liver test abnormalities or to clinically apparent liver injury. The reason for its safety may relate its use in low dose for short periods only.
Likelihood score: E (unlikely to be a cause of clinically apparent liver injury).
References on the safety and potential hepatotoxicity of antihistamines are given together after the Overview section on Antihistamines.
Drug Class: Antihistamines

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Small, occasional doses of triprolidine would not be expected to cause any adverse effects in breastfed infants. Larger doses or more prolonged use may cause effects in the infant or decrease the milk supply, particularly in combination with a sympathomimetic such as pseudoephedrine or before lactation is well established. The nonsedating antihistamines are preferred alternatives.
◉ Effects in Breastfed Infants
In one telephone follow-up study, mothers reported irritability and colicky symptoms 10% of infants exposed to various antihistamines and drowsiness was reported in 1.6% of infants. None of the reactions required medical attention and none of the mothers were taking triprolidine.
In one study, no infant side effects were reported in three infants whose mothers took one dose of triprolidine 2.5 mg and pseudoephedrine 60 mg.
◉ Effects on Lactation and Breastmilk
Antihistamines in relatively high doses given by injection can decrease basal serum prolactin in nonlactating women and in early postpartum women. However, suckling-induced prolactin secretion is not affected by antihistamine pretreatment of postpartum mothers. Whether lower oral doses of antihistamines have the same effect on serum prolactin or whether the effects on prolactin have any consequences on breastfeeding success have not been studied. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

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Interactions
Concurrent use /of ototoxic medications/ with antihistamines may mask the symptoms of ototoxicity such as tinnitus, dizziness, or vertigo. /Antihistamines/
Concurrent use of monoamine oxidase (MAO) inhibitors with antihistamines may prolong and intensify the anticholinergic and CNS depressant effects of antihistamines; concurrent use is not recommended. /Antihistamines/
Concurrent use /with alcohol or other CNS depression-producing medications/ may potentiate the CNS depressant effects of either these medications or antihistamines; also, concurrent use of maprotiline or tricyclic antidepressants may potentiate the anticholinergic effects of either antihistamines or these medications. /Antihistamines/
Anticholinergic effects may be potentiated when /anticholinergics or other medications with anticholinergic activity/ are used concurrently with antihistamines; patients should be advised to report occurrence of gastrointestinal problems promptly since paralytic ileus may occur with concurrent therapy. /Antihistamines/
For more Interactions (Complete) data for TRIPROLIDINE (10 total), please visit the HSDB record page.

[1]. Szeberényi JB, et, al. Inhibition of effects of endogenously synthesized histamine disturbs in vitro human dendritic cell differentiation. Immunol Lett. 2001 Apr 2;76(3):175-82.
[2]. Tzeng JI, et, al. Spinal sensory and motor blockade by intrathecal doxylamine and triprolidine in rats. J Pharm Pharmacol. 2018 Dec;70(12):1654-1661.
[3]. Deal DL, Chandrasurin P, Shockcor J, Minick DJ, Findlay JW, McNulty MJ. Disposition and metabolism of triprolidine in mice. Drug Metab Dispos. 1992 Nov-Dec;20(6):920-7.

Triprolidine is an N-alkylpyrrolidine that is acrivastine in which the pyridine ring is lacking the propenoic acid substituent. It is a sedating antihistamine that is used (generally as the monohydrochloride monohydrate) for the relief of the symptoms of uticaria, rhinitis, and various pruritic skin disorders. It has a role as a H1-receptor antagonist. It is a N-alkylpyrrolidine, a member of pyridines and an olefinic compound. It is a conjugate base of a triprolidine(1+).
First generation histamine H1 antagonist used in allergic rhinitis; asthma; and urticaria. It is a component of cough and cold medicines. It may cause drowsiness.
Triprolidine is a first generation antihistamine that is used for symptoms of allergic rhinitis and the common cold and as a short acting sedative. Triprolidine has not been linked to instances of clinically apparent acute liver injury.
Histamine H1 antagonist used in allergic rhinitis; ASTHMA; and URTICARIA. It is a component of COUGH and COLD medicines. It may cause drowsiness.
See also: Triprolidine Hydrochloride (has salt form) ... View More ...

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Drug Indication
For the symptomatic relief of seasonal or perennial allergic rhinitis or nonallergic rhinitis; allergic conjunctivitis; and mild, uncomplicated allergic skin manifestations of urticaria and angioedema. Also used in combination with other agents for the symptomatic relief of symptoms associated with the common cold.

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Mechanism of Action
Triprolidine binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine.
Antihistamines used in the treatment of allergy act by competing with histamine for H1-receptor sites on effector cells. They thereby prevent, but do not reverse, responses mediated by histamine alone. Antihistamines antagonize, in varying degrees, most of the pharmacological effects of histamine, including urticaria and pruritus. Also, the anticholinergic actions of most antihistamines provide a drying effect on the nasal mucosa. /Antihistamines/
Antihistamines used in the treatment of allergy act by competing with histamine for H1-receptor sites on effector cells. They thereby prevent, but do not reverse, responses mediated by histamine alone. Antihistamines antagonize, in varying degrees, most of the pharmacological effects of histamine, including urticaria and pruritus. Also, the anticholinergic actions of most antihistamines provide a drying effect on the nasal mucosa. /Antihistamines/
H1 antagonists inhibit most responses of smooth muscle to histamine. Antagonism of the constrictor action of histamine on respiratory smooth muscle is easily shown in vivo and in vitro. /Histamine Antagonists: H1 Antagonists/
/SRP:/ The action of histamine results in increased permeability and formation of edema and wheal. H1 antagonists block that action.
For more Mechanism of Action (Complete) data for TRIPROLIDINE (7 total), please visit the HSDB record page.

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Therapeutic Uses
Anti-Allergic Agents; Histamine H1 Antagonists
Antihistamines are indicated in the prophylactic and symptomatic treatment of perennial and seasonal allergic rhinitis, vasomotor rhinitis, and allergic conjunctivitis due to inhalant allergens and foods. /Antihistamines; Included in US product labeling/
Antihistamines are indicated for the symptomatic treatment of pruritus associated with allergic reactions and of mild, uncomplicated allergic skin manifestations of urticaria and angioedema, in dermatographism, and in urticaria associated with transfusions. /Antihistamines; Included in US product labeling/
Antihistamines are also used in the treatment of pruritus associated with pityriasis rosea. /Antihistamines; NOT included in US product labeling/
For more Therapeutic Uses (Complete) data for TRIPROLIDINE (8 total), please visit the HSDB record page.

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Drug Warnings
Use is not recommended in newborn or premature infants because this age group has an increased susceptibility to anticholinergic side effects, such as central nervous system excitation, and an increased tendency toward convulsions. A paradoxical reaction characterized by hyperexcitability may occur in children taking antihistamines. /Antihistamines/
Dizziness, sedation, confusion, and hypotension may be more likely to occur in geriatric patients taking antihistamines. Geriatric patients are especially susceptible to the anticholinergic side effects, such as dryness of mouth and urinary retention (especially in males), of the antihistamines. If these side effects occur and continue or are severe, medication should probably be discontinued. /Antihistamines/
Prolonged use of antihistamines ... may decrease or inhibit salivary flow, thus contributing to the development of caries, periodontal disease, oral candidiasis, and discomfort. /Antihistamines/
Maternal Medication usually Compatible with Breast-Feeding: Triprolidine: Reported Sign or Symptom in Infant or Effect on Lactation: None. /From Table 6/
For more Drug Warnings (Complete) data for TRIPROLIDINE (10 total), please visit the HSDB record page.

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Pharmacodynamics
In allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Triprolidine, is a histamine H1 antagonist that competes with histamine for the normal H1-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies. Triprolidine has anticholinergic and sedative effects.

C19H22N2

278.39

278.178

486-12-4

Triprolidine hydrochloride monohydrate;6138-79-0;(E/Z)-Triprolidine-d8 hydrochloride;1795134-06-3;Triprolidine hydrochloride;550-70-9

5282443

Crystals from light petroleum

1.061 g/cm3

435.4ºC at 760 mmHg

126-130°C

217.1ºC

6.16E-09mmHg at 25°C

3.855

0

2

4

21

336

0

CC1=CC=C(C=C1)/C(=C\CN2CCCC2)/C3=CC=CC=N3

CBEQULMOCCWAQT-WOJGMQOQSA-N

InChI=1S/C19H22N2/c1-16-7-9-17(10-8-16)18(19-6-2-3-12-20-19)11-15-21-13-4-5-14-21/h2-3,6-12H,4-5,13-15H2,1H3/b18-11+

2-[(E)-1-(4-methylphenyl)-3-pyrrolidin-1-ylprop-1-enyl]pyridine

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.)