In primary human gingival fibroblasts, tetrahydrozoline (0.05% HCl-tetrahydrozoline diluted to 1:20 concentration in DMEM; 24 hours) stimulates the synthesis of type I and type III collagen [3].

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- Primary human gingival fibroblasts (HGFs) were treated with tetrahydrozoline at concentrations of 0.1 μM, 1 μM, and 10 μM for 24 hours and 48 hours. After treatment, cell viability was evaluated using a colorimetric assay, and it was found that tetrahydrozoline significantly reduced HGF viability in a concentration-dependent manner; specifically, the 10 μM concentration caused a more than 50% decrease in viability after 48 hours of exposure. Additionally, tetrahydrozoline treatment led to a significant increase in the number of apoptotic HGFs, as detected by flow cytometry, and also downregulated the expression of collagen type I mRNA (measured by RT-PCR) and protein (measured by Western blot) in HGFs, with the downregulation effect being more obvious at higher concentrations and longer treatment times. [3]

Absorption, Distribution and Excretion
Following oral administration, Tetryzoline is rapidly absorbed from the gastrointestinal tract and crosses the blood-brain barrier. Peak plasma concentrations (Cmax) after ocular instillation of 0.05% Tetryzoline range from 0.068 to 0.380 ng/mL. Tetryzoline is detectable in urine 24 hours after ocular instillation of 0.05% Tetryzoline. No further information is available. Background: Tetryzoline (THZ) overdose in children can cause severe symptoms requiring intensive care. We report three cases of central nervous system depression and cardiovascular effects, and serum drug concentrations were measured. Case Reports: Case 1 ingested an unknown dose of eye drops containing a thiazide diuretic (THZ), resulting in altered mental status, bradycardia, hypothermia, and hypotension. Cases 2 and 3 ingested 7.5 mL of eye drops containing a thiazide diuretic. Case 2 presented to the emergency department asymptomatic, but developed drowsiness and bradycardia 90 minutes after ingestion. In contrast, Case 3 developed drowsiness 15 minutes after ingestion and required intubation upon arrival at the emergency department. All children were admitted to the intensive care unit (ICU) for observation and their conditions improved within 24 hours of ingestion. Urine drug screening results showed a positive result for thiazide diuretics. Blood samples were collected, and their concentrations were determined using gas chromatography-mass spectrometry (GC-MS). Case discussion: In Case 1, the plasma concentrations at 7 and 12 hours after Tetryzoline ingestion were 51.4 ng/mL and 23.6 ng/mL, respectively, with a half-life of 4.4 hours. Numerous case reports document the risks of ingesting these over-the-counter topical medications. However, there are currently no human pharmacokinetic data, therefore we cannot understand the toxicokinetics and distribution of Tetryzoline in humans after ingestion. Conclusion: We report three cases of children ingesting Tetryzoline, one of which had a plasma concentration with a calculated half-life of 4.4 hours.
Introduction: There is currently no information on therapeutic or toxic concentrations of Tetryzoline, which has been reported for use in adjunctive sexual assault. The primary objective of this study was to establish baseline therapeutic serum and urinary concentrations in a cohort of healthy volunteers. Methods: Ten healthy volunteers consented to the intraconjunctival instillation of two drops of unadulterated Visine eye drops (0.05% Tetryzoline solution) into the conjunctival sac of each eye at 0, 4, 8, and 12 hours. Blood and urine samples were subsequently collected at 2, 5, 9, 13, and 24 hours after administration, and their concentrations were analyzed. Central tendency and dispersion indices were used to describe Tetryzoline concentrations at each time point, and linear mixed-effects regression models were used to predict changes in serum and urinary Tetryzoline concentrations over time. Results: Tetryzoline was detectable in both serum and urine following therapeutic ocular administration. The mean serum half-life of Tetryzoline is approximately 6 hours. Systemic absorption varies from person to person, with maximum serum concentrations ranging from 0.068 to 0.380 ng/mL. Tetryzoline was detectable in the urine of all patients 24 hours later (range: 13-210 ng/mL). Conclusion: When used for ocular treatment as directed by the manufacturer, Tetryzoline is detectable in both serum and urine within 12 hours of the last dose. Concentrations significantly exceeding the 95% confidence interval for ocular treatment may indicate illegal adulteration or accidental/suicidal overdose. Topical application of Tetryzoline hydrochloride solution to the conjunctiva typically results in local vasoconstriction within minutes and can last for 4-8 hours. Occasionally, the absorbed amount of Tetryzoline may be sufficient to produce systemic effects. Information regarding the distribution and elimination of this drug in humans is currently unavailable. Metabolites/Metabolites: No relevant information available.

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Biological Half-Life
The average serum half-life after intraocular instillation of 0.05% Tetryzoline is approximately 6 hours.
...Ten healthy volunteers consented to have two drops of unopened Visine eye drops (0.05% Tetryzoline solution) instilled directly into the conjunctival sac of each eye at 0, 4, 8, and 12 hours, 30 seconds apart. Blood and urine samples were subsequently collected at 2, 5, 9, 13, and 24 hours after administration, and their concentrations were analyzed. ...The average serum half-life of Tetryzoline is approximately 6 hours. One child accidentally ingested an unknown dose of Tetryzoline (THZ)-containing eye drops; at 7 and 12 hours, the plasma THZ concentrations were 51.4 ng/mL and 23.6 ng/mL, respectively, with a half-life of 4.4 hours.

Toxicity Summary
Identification and Uses: Tetryzoline hydrochloride is an imidazoline derivative used for topical ocular treatment to temporarily relieve congestion, itching, and mild irritation, and to control congestion in patients with superficial corneal angiogenesis. Ocular decongestants are ineffective against delayed-type hypersensitivity reactions (e.g., contact dermatoconjunctivitis). The vasoconstrictive effect of Tetryzoline can be used in certain ophthalmic diagnostic procedures, but some clinicians prefer to use phenylephrine instead of Tetryzoline for such procedures. Human Studies: Serious adverse events requiring hospitalization have been reported in children who accidentally ingested over-the-counter ophthalmic solutions or nasal sprays containing imidazoline derivatives, including Tetryzoline. Between 1985 and October 2012, 96 cases of accidental ingestion of this drug in children aged 1 month to 5 years were reported. The intake ranged from 0.6 to 45 ml. Although no deaths were reported, more than half of the cases reported serious adverse reactions requiring hospitalization, including nausea, vomiting, somnolence, tachycardia, bradycardia, hypotension, hypertension, sedation, drowsiness, dilated pupils, coma, hypothermia, salivation, and coma. Animal studies: In canine poisoning, symptoms may include vomiting, bradycardia, arrhythmias, prolonged capillary refill time, hypotension or hypertension, wheezing, increased upper respiratory sounds, depression, weakness, nervousness, hyperactivity, or tremors. These symptoms appear between 30 minutes and 4 hours after exposure. Generally, exposure to imidazoline decongestants may affect the gastrointestinal, cardiopulmonary, and nervous systems. Protein binding: No relevant information available. Interactions: Background: We report two cases of drug-assisted sexual assault in which the victims experienced central nervous system depression, making them vulnerable to sexual assault and unable to recall events before and after the crime. Tetrahydroazoline (THZ) was detected in both cases. Case Report: Case 1: The patient ingested eye drops containing tetrahydroazoline (THZ) and mixed it with an alcoholic beverage. Case 1 reportedly presented to the emergency department approximately 7 hours after the alleged sexual assault, without any symptoms at the time of arrival. Witnesses had previously stated that the victim was "severely intoxicated." Case 2: The patient also ingested eye drops containing tetrahydroazoline (THZ) and mixed it with an alcoholic beverage. Case 2 presented to the emergency department approximately 23 hours after the alleged sexual assault, without any symptoms at that time. Tetrahydronaphthalene (THZ) concentrations in urine were measured in both cases using gas chromatography-mass spectrometry. Case Discussion: In Case 1, approximately 7 hours after THZ ingestion, the urine ethanol concentration was 0.15 g% (weight/volume), and the THZ concentration was 1.481 ng/mL. In Case 2, 23 hours after THZ ingestion, the urine ethanol test was negative, but the THZ concentration was 108 ng/mL. There are very few published case reports of THZ use to assist in sexual assault. Conclusion: We report two cases of THZ use to assist in sexual assault, both of which involved the consumption of alcoholic beverages. To our knowledge, this is the first paper to explore the pharmacology of Tetryzoline (THZ) intake and its significance in coexistence with alcohol. Long-term topical ophthalmic use of Tetryzoline is associated with anterior and posterior segment vascular lesions in human patients. Clinical manifestations include retinal artery occlusion (branch retinal artery occlusion and central retinal artery occlusion), retinal vein congestion, optic disc edema, and anterior segment signs such as corneal edema and anterior chamber inflammation. All patients had a history of regular Tetryzoline use for at least 6 months (reportedly 1-4 times daily), and some patients experienced improvement in visual function after discontinuation, while others had persistent visual impairment. [1]

[1]. E Kisilevsky, et al. Anterior and posterior segment vasculopathy associated with long-term use of tetrahydrozoline. CMAJ. 2018 Oct 9;190(40):E1208.
[2]. Judy Peat, et al.Determination of tetrahydrozoline in urine and blood using gas chromatography-mass spectrometry (GC-MS). Methods Mol Biol. 2010;603:501-8.
[3]. Danuta Nowakowska, et al. In vitro effects of vasoconstrictive retraction agents on primary human gingival fibroblasts. Exp Ther Med. 2020 Mar; 19(3): 2037-2044.

Tetryzoline belongs to the imidazoline and carboxymidin classes of compounds. It is a sympathomimetic drug and nasal decongestant. It is the conjugate base of Tetryzoline (1+). Tetryzoline, also known as Tetryzoline, is a derivative of imidazoline with central and peripheral alpha-adrenergic properties. Tetryzoline has been used since the 1950s as a selective α1-receptor agonist for ocular and nasal decongestion. Tetryzoline is found in a variety of over-the-counter eye drops, including the most common brand, Visine. Tetryzoline is also found in combination formulations with other lubricants and anti-irritants such as povidone, polyethylene glycol 400, dextran, and zinc sulfate. In other countries, Tetryzoline is also commonly used in combination with other medications such as antihistamines, corticosteroids, and glucocorticoids. Tetryzoline is also available under the brand name Tyzine in nasal sprays for relieving nasal and nasopharyngeal congestion. Because Tetryzoline can cause deep sedation in children and adults, there is growing concern about the potential for overdose and poisoning from accidental ingestion. Furthermore, it has been abused for non-therapeutic purposes, becoming a contributing factor in several cases of drug-assisted sexual assault. Tetryzoline is an imidazole derivative with sympathomimetic activity. When applied topically to the eyes or nose, Tetryzoline binds to and activates α-adrenergic receptors, causing vasoconstriction and reducing nasal and ocular congestion. See also: Tetryzoline hydrochloride (in its salt form); Tetryzoline nitrate (its active ingredient). Indications: Tetryzoline is indicated for the temporary relief of mild eye irritation and redness, and can be used alone or in combination with other eye lubricants and anti-irritants. Tetryzoline is also indicated for the relief of nasal and nasopharyngeal congestion.
FDA Label
Mechanism of Action
Adrenergic receptors are G protein-coupled receptors (GPCRs) that regulate vascular tone: stimulation of α-1 adrenergic receptors causes vasoconstriction. Redness of the eyes and nasal congestion are usually caused by dilation of capillaries in the nasal cavity, conjunctiva, and cornea. Therefore, activation of α1 adrenergic receptors is associated with relief of eye irritation and nasal congestion symptoms. Tetryzoline is a selective agonist of α1 adrenergic receptors that causes vasoconstriction, thereby relieving eye and nasal symptoms.
Therapeutic Uses
Ophthalmic solutions; sympathomimetic drugs; nasal decongestants

/Clinical Trials/ ClinicalTrials.gov is a registry and results database that lists human clinical studies conducted worldwide and funded by public and private institutions. This website is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH).
Each record on ClinicalTrials.gov provides a summary of the study protocol, including the following: disease or condition; intervention (e.g., medical product, behavior, or procedure under investigation); study title, description, and design; participation requirements (eligibility criteria); study location; contact information for the study location; and links to relevant information from other health websites, such as MedlinePlus (for patient health information) and PubMed (for citations and abstracts of academic articles in the medical field) from the National Library of Medicine (NLM). Tetryzoline is included in the database.
Used to relieve redness of the eye caused by minor eye irritation. /US product label contains/
Tetryzoline hydrochloride is applied topically to the conjunctiva for self-medication to temporarily relieve congestion, itching, and minor irritation, and to control congestion in patients with superficial corneal vessels. Ocular decongestants are ineffective against delayed-type hypersensitivity reactions (e.g., contact dermatoconjunctivitis). The vasoconstrictive effect of Tetryzoline can be used in some ophthalmic diagnostic procedures, but some clinicians prefer to use phenylephrine instead of Tetryzoline for such procedures. For more complete data on the therapeutic uses of Tetryzoline (6 types), please visit the HSDB record page.

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Drug Warnings
Overuse and/or prolonged or excessively frequent use of Tetryzoline should be avoided. Overuse in children may cause severe drowsiness with profuse sweating.
Ophthalmic use of Tetryzoline may occasionally cause systemic sympathomimetic effects such as headache, hypertension, weakness, sweating, palpitations, and tremor. Overuse may cause central nervous system depression with drowsiness, hypothermia, bradycardia, shock-like hypotension, apnea, and coma.In pediatric patients, accidental ingestion of imidazoline derivatives (e.g., Tetryzoline, naphazoline, oxymetazoline) can lead to serious adverse events requiring hospitalization (e.g., coma, bradycardia, bradycardia, sedation, drowsiness).
Tetryzoline hydrochloride is contraindicated in children under 2 years of age. Children under 6 years of age should not self-medicate with Tetryzoline eye drops.
Tetryzoline used in the eyes may cause blurred vision, irritation, and mydriasis. Conjunctival application of Tetryzoline, especially in high concentrations in elderly patients, may lead to the release of pigment granules, presumably originating from the iris. Rebound congestion, characterized by chronic redness, swelling, or reactive congestion, is common with prolonged use. For these reasons, prolonged use of Tetryzoline eye drops should be avoided.
For more complete data on Tetryzoline (11 in total), please visit the HSDB record page.

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Pharmacodynamics
Tetryzoline is a sympathomimetic amine and an alpha-adrenergic agonist with vasoconstrictive and decongestant effects. It relieves allergic rhinitis, nasal congestion, and eye irritation by constricting small arteries in the nasal cavity and conjunctiva. Tetryzoline can cross the blood-brain barrier and act on α2-adrenergic receptors and imidazole receptors, producing hypotensive, bradycardic, analgesic, hypothermic, sedative, and hypnotic effects. Tetryzoline is a sympathomimetic drug with vasoconstrictive effects, commonly used in ophthalmic preparations to relieve redness of the eyes caused by conjunctival vasodilation. [1] Tetryzoline exerts its vasoconstrictive effect by activating α-adrenergic receptors on vascular smooth muscle cells, leading to vasoconstriction and reducing blood flow to target tissues (such as conjunctival or gingival vessels). [3]

C13H16N2

200.27954

200.131

84-22-0

Tetrahydrozoline hydrochloride;522-48-5;Tetrahydrozoline nitrate;118201-38-0

5419

White to off-white solid powder

1.2 g/cm3

393.5ºC at 760 mmHg

>250

191.8ºC

1.656

1.872

1

1

1

15

259

0

N1CCNC=1C1CCCC2C1=CC=CC=2

BYJAVTDNIXVSPW-UHFFFAOYSA-N

InChI=1S/C13H16N2/c1-2-6-11-10(4-1)5-3-7-12(11)13-14-8-9-15-13/h1-2,4,6,12H,3,5,7-9H2,(H,14,15)

2-(1,2,3,4-tetrahydronaphthalen-1-yl)-4,5-dihydro-1H-imidazole

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.)