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 intestine. H1 receptor antagonists are well absorbed in the gastrointestinal tract. Peak plasma concentrations are reached within 2 to 3 hours after oral administration, and the duration of action typically lasts 4 to 6 hours; however, some drugs have a longer duration of action… /Histamine Antagonists: H1 Receptor Antagonists/ …Children clear H1 receptor antagonists faster than adults, while clearance is slower in patients with severe liver disease. /Histamine Antagonists: H1 Receptor Antagonists/

---

Metabolism/Metabolites The primary site of metabolic transformation is the liver. /Antichrists/

---

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

Hepatotoxicity
As with most first-generation antihistamines, triprolidine has not been found to be associated with abnormal liver function or clinically significant liver injury. Its safety profile may be related to its use only at short-term, low-dose doses. Likelihood Score: E (Unlikely to cause clinically significant liver injury). References on the safety and potential hepatotoxicity of antihistamines are listed after the "Antihistamines Overview" section. Drug Category: Antihistamines Pregnancy and Lactation Effects ◉ Overview of Use During Lactation Low-dose, occasional use of triprolidine is not expected to have any adverse effects on breastfed infants. Higher doses or prolonged use may affect the infant or reduce milk production, especially when used in combination with sympathomimetic drugs (such as pseudoephedrine) or before lactation is fully established. Non-sedating antihistamines are a better option.
◉ Effects on Breastfed Infants
In a telephone follow-up study, mothers reported that 10% of infants exposed to various antihistamines experienced irritability and colic, and 1.6% experienced lethargy. All adverse reactions were painless and none of the mothers were taking triprolidine.
In one study, three mothers received a single dose of 2.5 mg triprolidine and 60 mg pseudoephedrine, and no adverse effects were reported in their infants.
◉ Effects on Lactation and Breast Milk
Higher doses of injected antihistamines can lower basal serum prolactin levels in non-lactating women and early postpartum women. However, pre-administration of antihistamines by postpartum mothers does not affect lactation-induced prolactin secretion. Whether low-dose oral antihistamines have the same effect on serum prolactin levels, and whether their effect on prolactin has any impact on breastfeeding success, is currently unstudied. Prolactin levels in established lactating mothers may not affect their ability to breastfeed.

---

Drug Interactions
Concomitant use of antihistamines with ototoxic drugs may mask ototoxic symptoms such as tinnitus, dizziness, or vertigo. Antihistamines
Concomitant use of antihistamines with monoamine oxidase (MAO) inhibitors may prolong and enhance the anticholinergic and central nervous system depressant effects of antihistamines; concomitant use is not recommended. Antihistamines
Concomitant use of antihistamines with alcohol or other central nervous system depressants may enhance the central nervous system depressant effects of these drugs or antihistamines; in addition, concomitant use of maprotiline or tricyclic antidepressants may enhance the antihistamine or anticholinergic effects of these drugs. /Antihistamines/
When /anticholinergic drugs or other drugs with anticholinergic activity/ are used concomitantly with antihistamines, the anticholinergic effect may be enhanced; patients should be advised to report gastrointestinal problems promptly, as concomitant treatment may lead to paralytic ileus. /Antichristants/
For more complete data on drug interactions of triprolidine (10 drugs in 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.

Triptoridine is an N-alkylpyrrolidine compound, a derivative of acristatin, lacking the acrylic acid substituent on its pyridine ring. It is a sedative antihistamine, usually used in its hydrochloride monohydrate form to relieve symptoms of urticaria, rhinitis, and various pruritic skin conditions. It is an H1 receptor antagonist. It is an N-alkylpyrrolidine compound belonging to the pyridine and olefin classes. It is the conjugate base of triploridine (1+). A first-generation histamine H1 receptor antagonist used to treat allergic rhinitis, asthma, and urticaria. It is an ingredient in cough and cold medicines. It may cause drowsiness. Triptoridine is a first-generation antihistamine used to treat symptoms of allergic rhinitis and the common cold, and can be used as a short-acting sedative. No clinically significant cases of acute liver injury have been found associated with triploridine. Triptoridine is a histamine H1 receptor antagonist used to treat allergic rhinitis, asthma, and urticaria. It is an ingredient in cold and cough medicines. It may cause drowsiness.
See also: Triptoridine hydrochloride (salt form)...See more...
Drug Indications

For the relief of symptoms of seasonal or perennial allergic rhinitis or non-allergic rhinitis, allergic conjunctivitis, and mild, uncomplicated allergic skin manifestations (urticaria and angioedema). It may also be used in combination with other medications to relieve symptoms associated with the common cold.
Mechanism of Action

Triporidine binds to histamine H1 receptors. This blocks the action of endogenous histamine, thereby temporarily relieving the adverse symptoms caused by histamine.
Antihistamines used to treat allergies act by competing with histamine for H1 receptor sites on effector cells. They can prevent but not reverse reactions mediated solely by histamine. Antihistamines antagonize most of the pharmacological effects of histamine to varying degrees, including urticaria and itching. In addition, the anticholinergic effects of most antihistamines can also cause nasal dryness. /Antichrists/
Antichrists used to treat allergies act by competing with histamine for H1 receptor sites on effector cells. They can prevent but not reverse reactions mediated solely by histamine. Antihistamines antagonize most of the pharmacological effects of histamine to varying degrees, including urticaria and pruritus. In addition, the anticholinergic effects of most antihistamines can cause dryness of the nasal mucosa. /Antichrists/
H1 receptor antagonists inhibit most of the smooth muscle response to histamine. Their antagonism of the contractile effect of histamine on respiratory smooth muscle is readily demonstrated in both in vivo and in vitro studies. /Histamine Antagonists: H1 Receptor Antagonists/
/SRP:/ The effects of histamine lead to increased permeability and the formation of edema and wheals. H1 receptor antagonists block this effect.
For more complete data on the mechanisms of action of triprolidine (7 types), please visit the HSDB record page.

---

Therapeutic Use
Antihistamine; Histamine H1 Receptor Antagonist
Antihistamines are indicated for the prevention and treatment of perennial and seasonal allergic rhinitis, vasomotor rhinitis, and allergic conjunctivitis caused by inhaled allergens and foods. /Antihistamines; included on the US product label/
Antihistamines are indicated for the treatment of itching associated with allergic reactions, as well as mild, uncomplicated allergic skin manifestations such as urticaria and angioedema, dermatographia, and transfusion-associated urticaria. /Antihistamines; included on the US product label/
Antihistamines are also used to treat itching associated with pityriasis rosea. /Antihistamines; not included on the US product label/
For more complete data on the therapeutic uses of triprolidine (8 types), please visit the HSDB record page.

---

Drug Warnings
Not recommended for use in newborns or premature infants, as this age group is more sensitive to anticholinergic side effects (such as central nervous system excitation) and more prone to seizures. Children taking antihistamines may experience paradoxical reactions characterized by hyperexcitability. /Anthistamines/
Elderly patients are more likely to experience dizziness, sedation, confusion, and hypotension after taking antihistamines. Elderly patients are particularly susceptible to the anticholinergic side effects of antihistamines, such as dry mouth and urinary retention (especially in men). If these side effects occur and persist or are severe, discontinuation of the medication should be considered. /Anthistamines/
Prolonged use of antihistamines…may reduce or inhibit saliva production, leading to dental caries, periodontal disease, oral candidiasis, and discomfort. /Anthistamines/
Mostly compatible with breastfeeding maternal use: Triptoridine: Signs or symptoms reported by the infant or effects on lactation: None. /Excerpt from Table 6/
For more complete data on drug warnings for Triptoridine (10 of them), please visit the HSDB record page.

---

Pharmacodynamics
In allergic reactions, allergens interact with and cross-link with IgE antibodies on the surface of mast cells and basophils. Once a mast cell-antibody-antigen complex is formed, a series of complex events occur, ultimately leading to cell degranulation and the release of histamine (and other chemical mediators) from mast cells or basophils. After histamine release, it can react with local or systemic tissues via histamine receptors. Histamine acts on H1 receptors, causing itching, vasodilation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine can also increase vascular permeability and exacerbate pain. Triptloridine is a histamine H1 receptor antagonist that competes with histamine for normal H1 receptor sites on effector cells in the gastrointestinal tract, blood vessels, and respiratory tract. Triptloridine can effectively and temporarily relieve symptoms such as sneezing, tearing, itchy eyes, and runny nose caused by hay fever and other upper respiratory tract allergies. Triptloridine 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.

---

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).

View More

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)

---

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).

View More

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

---

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.

---

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