在原代人牙龈成纤维细胞中，四氢唑啉（0.05% HCl-四氢唑啉在 DMEM 中稀释至 1:20 浓度；24 小时）刺激 I 型和 III 型胶原蛋白的合成 [3]。

Absorption, Distribution and Excretion
When consumed orally, tetryzoline is rapidly absorbed from the gastrointestinal tract and can cross the blood-brain barrier. Following ocular administration of 0.05% tetryzoline, Cmax ranged from 0.068 to 0.380 ng/mL.
Following ocular administration of 0.05% tetryzoline, tetryzoline was detected in urine at 24 hours.
No information is available.
No information is available.
BACKGROUND: Major symptoms can occur from tetrahydrozoline (THZ) overdoses in young children, requiring intensive care management. We report three cases that presented with CNS depression and cardiovascular effects where serum concentrations were performed. CASE REPORT: Case 1 ingested an unknown amount of eye drops containing THZ, resulting in altered mental status, bradycardia, hypothermia, and hypotension. Cases 2 and 3 ingested 7.5 mL of eye drops containing THZ. Case 2 presented to the emergency department (ED) without symptoms but became lethargic and bradycardic 90 min after ingestion. By contrast, Case 3 became lethargic 15 min after ingestion and required intubation on arrival to the ED. All children were admitted to ICU for observation and improved within 24 hr of ingestion. Urine obtained for drug screening was positive for THZ. Blood was obtained to assess level using gas-chromatography mass-spectrometry (GC-MS). CASE DISCUSSION: Case 1 had plasma levels of 51.4 and 23.6 ng/mL at 7 and 12 hr, respectively, after ingestion, revealing a half-life of 4.4 hr. Numerous case reports have been published documenting the dangers of ingesting these topical over-the-counter (OTC) products. However, human PK data are not available to help in our understanding of THZ toxicokinetics and disposition in humans after ingestion. CONCLUSION: We report three pediatric cases after ingestion of THZ where plasma concentrations were obtained with a calculated half-life of 4.4 hr in one case.
INTRODUCTION: No information exists on therapeutic or toxic concentrations of tetrahydrozoline, which has been reported to be used in drug facilitated sexual assaults. The primary aim of this investigation was to establish baseline therapeutic serum and urine concentrations in a sample of healthy volunteers. METHODS: Ten healthy volunteers consented to have two drops of Original Visine eye drops (0.05% tetrahydrozoline solution) placed directly into the conjunctival sac of each eye, 30 seconds apart, at times 0, 4, 8, and 12 hr. Blood and urine samples were then collected at 2, 5, 9, 13, and 24 hr post-application and analyzed for concentrations. Tetrahydrozoline concentrations are described using measures of central tendency and dispersion at each time point, with predictions of serum and urine concentrations over time calculated using a linear mixed effects regression model. RESULTS: Tetrahydrazoline concentrations were detectable in both serum and urine after therapeutic ocular administration. The mean serum half-life of tetrahydrozoline was approximately 6 hr. Systemic absorption varied among subjects, with the maximum serum concentrations ranging from 0.068 to 0.380 ng/mL. At 24 hr, all patients had detectable urine concentrations of tetrahydrozoline (range = 13-210 ng/mL). CONCLUSION: When used as directed by the manufacturer for therapeutic ocular administration, tetrahydrozoline concentrations were detectable in both serum and urine up to 12 hr after the last administered dose. A concentration greatly exceeding the 95% confidence interval of drug present during therapeutic ocular use may be suggestive of illegal adulterant use or accidental or suicidal overdose.
Following topical application of tetrahydrozoline hydrochloride solutions to the conjunctiva, local vasoconstriction usually occurs within a few minutes and may persist for 4-8 hours. Occasionally, enough tetrahydrozoline may be absorbed to produce systemic effects. Information on the distribution and elimination of the drug in humans is not available.

---

Metabolism / Metabolites
No information is available.

---

Biological Half-Life
Following ocular administration of 0.05% tetryzoline, the mean serum half-life was approximately 6 hours.
... Ten healthy volunteers consented to have two drops of Original Visine eye drops (0.05% tetrahydrozoline solution) placed directly into the conjunctival sac of each eye, 30 seconds apart, at times 0, 4, 8, and 12 hr. Blood and urine samples were then collected at 2, 5, 9, 13, and 24 hr post-application and analyzed for concentrations. ... The mean serum half-life of tetrahydrozoline was approximately 6 hr. ...
/A child/ ingested an unknown amount of eye drops containing tetrahydrozoline (THZ) ... had plasma levels of 51.4 and 23.6 ng/mL at 7 and 12 hr, respectively, after ingestion, revealing a half-life of 4.4 hr. ...

Toxicity Summary
IDENTIFICATION AND USE: Tetrahydrozoline hydrochloride, an imidazoline derivative, is applied topically to the eye for self-medication to temporarily relieve congestion, itching, and minor irritation, and to control hyperemia in patients with superficial corneal vascularity. Ocular decongestants are ineffective in the treatment of delayed hypersensitivity reactions such as contact dermatoconjunctivitis. The vasoconstrictor effect of tetrahydrozoline may be used during some ocular diagnostic procedures, but some clinicians prefer phenylephrine to tetrahydrozoline for this use. HUMAN STUDIES: Serious adverse events requiring hospitalization have been reported in pediatric patients following accidental ingestion of nonprescription ophthalmic solutions or nasal sprays containing imidazoline derivatives including tetrahydrozoline. Between 1985 and October 2012, 96 cases of accidental ingestion were reported in children 1 month to 5 years of age. The amount of drug ingested ranged from 0.6-45 mL. While no deaths were reported, more than half of these cases reported serious adverse events requiring hospitalization, including nausea, vomiting, lethargy, tachycardia, decreased respiration, bradycardia, hypotension, hypertension, sedation, somnolence, mydriasis, stupor, hypothermia, drooling, and coma. ANIMAL STUDIES: In dogs, signs of intoxication may include vomiting, bradycardia, cardiac arrhythmias, poor capillary refill time, hypotension or hypertension, panting, increased upper respiratory sounds, depression, weakness, nervousness, hyperactivity, or shaking. These signs appear within 30 min to 4 hr postexposure. In general, imidazoline decongestant exposure may affect the GI, cardiopulmonary, and nervous systems.

---

Protein Binding
No information is available.

---

Interactions
BACKGROUND: We report two cases of drug-facilitated sexual assault which presented with CNS depression rendering the victims vulnerable to sexual assault and unable to recall the events surrounding the crimes. In each tetrahydrozoline (THZ) was quantified. CASE REPORT: Case #1 ingested an unknown amount of eye drops containing THZ mixed with alcoholic beverages. Case #1 presented to the emergency department (ED) approximately 7 hr after reportedly being sexually assaulted and was without symptoms in the ED. Earlier reports from individuals who saw her indicated the victim to be "heavily intoxicated". Case #2 also ingested an unknown amount of eye drops containing THZ mixed with alcoholic beverages. Case #2 presented to an ED without symptoms approximately 23 hr after reportedly being sexually assaulted. Urine obtained from both cases was assessed for THZ concentrations using gas-chromatography-mass spectrometry. CASE DISCUSSION: Case #1 had a 0.15 g% (by weight by volume) urine ethanol concentration and a urinary THZ concentration of 1.481 ng/mL, approximately 7h after ingestion. Case #2 was negative for ethanol but had a urine THZ concentration of 108 ng/mL at 23 hr post-ingestion. Few case reports have been published documenting the use of THZ to facilitate sexual assault. CONCLUSION: We report two cases of drug-facilitated sexual assault involving the use of THZ where alcoholic beverages were concomitantly consumed. This is the first paper to our knowledge which discusses pharmacology of THZ ingestion and the significance of alcohol being present.

[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 is a member of imidazolines and a carboxamidine. It has a role as a sympathomimetic agent and a nasal decongestant. It is a conjugate base of a tetryzoline(1+).
Tetryzoline, also known as tetrahydrozoline, is a derivative of imidazoline with central and peripheral alpha (α)-adrenergic properties. Available since the 1950s, tetryzoline is a selective α1-receptor agonist that is used as an ocular and nasal decongestant. Tetryzoline is found in a wide array of over-the-counter eye drops, including the most common brand, Visine. Tetryzoline is also found in combination products with other lubricants and anti-irritants, such as [povidone], [polyethylene glycol 400], [dextran], and [zinc sulfate]. It is also used in combination with other drug classes, such as antihistamines, corticosteroids, and glucocorticoids in other countries. Tetryzoline is also found in nasal spray under the trade name Tyzine, which is used for decongestion of nasal and nasopharyngeal mucosa. As it causes profound sedation in children and adults, tetryzoline is increasingly becoming scrutinized for possible drug overdose and toxicity from accidental ingestion. It has also been misused for non-therapeutic purposes as a causative drug for several cases of drug-facilitated sexual assault.
Tetrahydrozoline is an imidazole derivative with sympathomimetic activity. Applied locally to the eye or nose, tetrahydrozoline binds to and activates alpha-adrenergic receptors, resulting in vasoconstriction and decreased nasal and ophthalmic congestion.
See also: Tetrahydrozoline Hydrochloride (has salt form); Tetrahydrozoline Nitrate (is active moiety of).

---

Drug Indication
Tetryzoline is indicated for the temporary relief of discomfort and redness of the eye due to minor eye irritations as monotherapy or in combination with other eye lubricants and anti-irritants. Tetryzoline is also indicated for decongestion of nasal and nasopharyngeal mucosa.
FDA Label

---

Mechanism of Action
Adrenergic receptors are G-protein-coupled receptors (GPCR) that regulate vascular tone: stimulation of alpha-1 adrenergic receptors leads to vasoconstriction. Ocular redness and nasal congestion often result from vasodilation of nasal, conjunctival, and corneal capillary blood vessels. Activation of alpha-1 adrenergic receptors have been therefore associated with a reduction of symptoms of ocular irritation and nasal congestion. Tetryzoline is a selective agonist of alpha-1 adrenergic receptors, causing vasoconstriction and alleviating ocular and nasal symptoms.

---

Therapeutic Uses
Ophthalmic Solutions; Sympathomimetics; Nasal Decongestants
/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Tetrahydrozoline is included in the database.
For the relief of redness of the eye due to minor eye irritations. /Included in US product label/
Tetrahydrozoline hydrochloride is applied topically to the conjunctiva for self-medication to temporarily relieve congestion, itching, and minor irritation, and to control hyperemia in patients with superficial corneal vascularity. Ocular decongestants are ineffective in the treatment of delayed hypersensitivity reactions such as contact dermatoconjunctivitis. The vasoconstrictor effect of tetrahydrozoline may be used during some ocular diagnostic procedures, but some clinicians prefer phenylephrine to tetrahydrozoline for this use.
For more Therapeutic Uses (Complete) data for Tetrahydrozoline (6 total), please visit the HSDB record page.

---

Drug Warnings
Excessive dosage and/or prolonged or too frequent use of tetrahydrozoline should be avoided. In children, excessive dosage of the drug may cause severe drowsiness accompanied by profuse sweating.
Ophthalmic use of tetrahydrozoline occasionally may cause systemic sympathomimetic effects such as headache, hypertension, weakness, sweating, palpitation, and tremors. Overdosage of the drug may produce CNS depression with drowsiness, decreased body temperature, bradycardia, shock-like hypotension, apnea, and coma. In pediatric patients, accidental ingestion of imidazoline derivatives (i.e., tetrahydrozoline, naphazoline, oxymetazoline) has resulted in serious adverse events requiring hospitalization (e.g., coma, bradycardia, decreased respiration, sedation, somnolence).
Tetrahydrozoline hydrochloride is contraindicated in children younger than 2 years of age. Ophthalmic solutions of tetrahydrozoline should not be used for self-medication in children younger than 6 years of age.
Use of tetrahydrozoline in the eye may cause blurred vision, irritation, and mydriasis. Conjunctival application of tetrahydrozoline, especially when high concentrations are used in geriatric patients, may liberate pigment granules, presumably from the iris. Rebound congestion, characterized by chronic redness, swelling, or reactive hyperemia, frequently occurs with prolonged use. Prolonged use of tetrahydrozoline ophthalmic solution should be avoided for these reasons.
For more Drug Warnings (Complete) data for Tetrahydrozoline (11 total), please visit the HSDB record page.

---

Pharmacodynamics
Tetryzoline is a sympathomimetic amine and an alpha-adrenergic agonist with vasoconstricting and decongestant properties. It works by constricting the smaller arterioles of the nasal passages and conjunctival blood vessels to ameliorate allergic rhinitis, nasal congestion, and ocular irritation. Tetryzoline is known to cross the blood-brain barrier to work on alpha-2 adrenoceptors and imidazole receptors, causing effects like hypotension, bradycardia, analgesia, hypothermia, sedation, and hypnosis.

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

24.39

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

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

---

注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

View More

注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

---

口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

View More

口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

---

注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

---

请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。