Absorption, Distribution and Excretion
Absorption is good in the digestive tract.
H1 receptor antagonists are well absorbed in the gastrointestinal tract. After oral administration, peak plasma concentrations are reached within 2 to 3 hours, and the effect typically lasts 4 to 6 hours; however, some drugs have a longer duration of action… /Histamine Antagonists: H1 Receptor Antagonists/
…H1 receptor antagonists are cleared faster in children than in adults, while clearance is slower in patients with severe liver disease. /Histamine Antagonists: H1 Receptor Antagonists/
Metabolism/Metabolites

Hepatitis
A minor metabolite, N-oxide, has been identified in the urine of people who have taken tripirenamine orally. The major conjugate is a unique quaternary ammonium N-glucuronide, and two other metabolites are hydroxylated derivatives of O-glucuronide. Hydroxytripirenamine glucuronide is the major metabolite.
The primary site of metabolic transformation is the liver. /Antichristants/
H1 receptor antagonists are among many drugs that can induce hepatic microsomal enzymes, which may promote their own metabolism. /Histamine antagonists: H1 antagonists/
Known human metabolites of tripermin include tripermin N-glucuronide.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Occasional use of small doses of tramapenamin is not expected to have any adverse effects on breastfed infants. Larger doses or prolonged use may cause infant drowsiness and other adverse reactions, 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 alternative.
◉ Effects on Breastfed Infants
As of the revision date, no published information was found regarding tramapenamin. In a telephone follow-up study, mothers reported irritability and colic in 10% of their infants after taking various antihistamines, and drowsiness in 1.6% of their infants. All reactions did not require medical attention.
◉ Effects on Lactation and Breast Milk
Higher doses of injected antihistamines can lower baseline serum prolactin levels in non-lactating women and early postpartum women. However, pre-administration of antihistamines by postpartum mothers does not affect suckling-induced prolactin secretion. Whether lower oral doses of antihistamines have the same effect on serum prolactin, 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 breastfeeding ability.

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Interactions
Concomitant use of ototoxic drugs and antihistamines may mask ototoxic symptoms such as tinnitus, dizziness, or vertigo. /Antihistamines/
Concomitant use of monoamine oxidase (MAO) inhibitors with antihistamines may prolong and enhance the anticholinergic and central nervous system depressant effects of antihistamines; concomitant use is not recommended. /Antihistamines/
Concomitant use with alcohol or other central nervous system depressants may enhance the central nervous system depressant effects of these drugs or antihistamines; furthermore, concomitant use with 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 in combination with antihistamines, the anticholinergic effect may be enhanced; patients should be advised to report gastrointestinal problems promptly, as co-use may lead to paralytic ileus. /Antihistamines/
For more complete data on interactions of tripirenamine (6 types), please visit the HSDB record page.

[1]. H1-receptor antagonist, tripelennamine, does not affect arterial hypoxemia in exercising Thoroughbreds. J Appl Physiol. 2002 Apr;92(4):1515-23.

[2]. Comparative disposition of tripelennamine in horses and camels after intravenous administration. J Vet Pharmacol Ther. 2000 Jun;23(3):145-52.

[3]. The pharmacokinetics of pentazocine and tripelennamine. Clin Pharmacol Ther. 1986 Jun;39(6):669-76.

Tripelenamine is an oily liquid with an amine odor. (NTP, 1992)
Tripelenamine is an aromatic amine.
It is a histamine H1 receptor antagonist with a weak sedative effect, but often causes gastrointestinal irritation. It is used to treat asthma, hay fever, urticaria, and rhinitis, and is also used in veterinary medicine. Tripelenamine can be administered via various routes, including topical application.
It is a histamine H1 receptor antagonist with a weak sedative effect, but often causes gastrointestinal irritation. It is used to treat asthma, hay fever, urticaria, and rhinitis, and is also used in veterinary medicine. Tripelenamine can be administered via various routes, including topical application.
See also: Tripelenamine hydrochloride (salt form); Tripelenamine citrate (salt form).
Indications: Used to relieve allergic reactions, cough, and common cold symptoms.
Mechanism of Action: Tripelenamine binds to histamine H1 receptors. This blocks the action of endogenous histamine, thus temporarily relieving the adverse symptoms caused by histamine. Antihistamines used to treat allergies work by competing with histamine for H1 receptor sites on effector cells. They can prevent (but cannot 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. /Anthistamines/
H1 receptor antagonists inhibit most of the smooth muscle response to histamine. Their effect on the histamine-induced contraction of respiratory smooth muscle is readily confirmed in both in vivo and in vitro experiments. /Histamine Antagonists: H1 Receptor Antagonists/
H1 receptor antagonists potently block the histamine-induced increase in vascular permeability and the formation of edema and wheals. /Histamine Antagonists: H1 Receptor Antagonists/
In the vascular system, H1 receptor antagonists inhibit both the vasoconstrictive effects of histamine and, to some extent, the more rapid vasodilation mediated by H1 receptors on endothelial cells. The residual vasodilation reflects the involvement of H2 receptors on smooth muscle and can only be inhibited by concurrent administration of H2 receptor antagonists. The effects of histamine antagonists on histamine-induced systemic blood pressure changes parallel these vascular effects. /Histamine Antagonists: H1 Receptor Antagonists/
Many H1 receptor antagonists tend to inhibit the acetylcholine response mediated by muscarinic receptors. These atropine-like effects of some drugs are significant enough to be observed in clinical applications… /Histamine Antagonists: H1 Receptor Antagonists/

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Therapeutic Uses
Antihistamine; Histamine H1 Receptor Antagonists
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 tripirenamine (8 types), please visit the HSDB record page.

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Drug Warnings
This medication is not recommended for use in newborns or premature infants because this age group is more sensitive to anticholinergic side effects (such as central nervous system excitation) and is more prone to seizures. Children taking antihistamines may experience paradoxical reactions characterized by hyperexcitability. /Anthistamines/
Older patients are more likely to experience dizziness, sedation, confusion, and hypotension when taking antihistamines. Older 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 tooth decay, periodontal disease, oral candidiasis, and discomfort. /Anthistamines/
Bioavailability of extended-release formulations may be neither uniform nor reliable. /Hydrochloride/
For more complete data on drug warnings for tropirenine (16 in total), please visit the HSDB record page.

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Pharmacodynamics
Used to treat cold and allergy symptoms. Tripirenine is an antihistamine. Histamine acts on H1 receptors, causing itching, vasodilation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and exacerbates pain. Tripirenine is a histamine H1 receptor antagonist. It competes with histamine for normal H1 receptor sites on effector cells in the gastrointestinal tract, blood vessels, and respiratory tract. It can effectively and temporarily relieve symptoms such as sneezing, watery and itchy eyes, and runny nose caused by hay fever and other upper respiratory allergies.

C16H22CLN3

291.82

255.174

91-81-6

Tripelennamine hydrochloride;154-69-8;Tripelennamine citrate;6138-56-3

5587

YELLOW OIL

1.0683 (rough estimate)

185 - 190ºC at 1.7 mm Hg

25°C

nD25 1.5759-1.5765

2.649

0

3

6

19

236

0

N1C(N(CCN(C)C)CC2C=CC=CC=2)=CC=CC=1

UFLGIAIHIAPJJC-UHFFFAOYSA-N

InChI=1S/C16H21N3/c1-18(2)12-13-19(16-10-6-7-11-17-16)14-15-8-4-3-5-9-15/h3-11H,12-14H2,1-2H3

N'-benzyl-N,N-dimethyl-N'-pyridin-2-ylethane-1,2-diamine

NSC-409943; NSC 409943; Cizaron, HSDB 5191, Tripelennamine

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.)