Antazoline targets the histamine H1 receptor, acting as a competitive antagonist. It also possesses anticholinergic properties. By blocking H1 receptors, it prevents histamine-induced vasodilation, increased vascular permeability, and smooth muscle contraction, which are key features of allergic reactions. Its anticholinergic effects may contribute to its action in the eye.

In the supernatant of HepAD38 and Huh7 cells, phenazoline exhibits a strong inhibitory impact on HBV DNA, with EC50 values of 2.910 μmol/L and 2.349 μmol/L, respectively [2].
In vitro, antazoline acts as a histamine H1 receptor antagonist. It can prevent histamine from acting on target cells through a reversible competition effect on histamine receptor sites. Its antiviral properties have also been demonstrated. These activities confirm its profile as an antihistamine with additional properties.

Antazoline (IP; 0.01 ml/g; 30 minutes), as an H1 receptor antagonist, attenuates the anticonvulsant action of carbamazepine and diphenylhydantoin [3].
In vivo, antazoline is used for local application to the eye in allergic conjunctivitis. It is usually used in combination with naphazoline to relieve the symptoms of allergic conjunctivitis. It relieves nasal congestion and is used in eye drops. Its topical use minimizes systemic side effects.

The in vitro receptor binding assay for antazoline typically involves radioligand displacement studies using membrane preparations from cells expressing the histamine H1 receptor. The compound's affinity is determined by measuring its ability to displace a specific radiolabeled ligand from the receptor. These cell-free assays provide a direct measure of the compound's binding affinity for the H1 receptor.

Cytotoxicity assay [2]
Cell Types: HepAD38 cells
Tested Concentrations: 10 μmol/L
Incubation Duration: 5 days
Experimental Results: There is no obvious cytotoxicity at the concentration of 10 μmol/L, and it has a dose-dependent inhibitory effect on HBV DNA in the supernatant.

---

RT-PCR[2]
Cell Types: Huh7 Cell
Tested Concentrations: 30 μmol/L, 10 μmol/L, 3.33 μmol/L, 1.1 μmol/L, 0.370 μmol/L and 0.123 μmol/L
Incubation Duration: 4 days
Experimental Results: Yes HBV DNA in the supernatant has a significant inhibitory effect in a dose-dependent manner.
In vitro cellular assays for antazoline assess its functional antagonism at the H1 receptor. Cells expressing the H1 receptor are stimulated with histamine, and the compound's ability to inhibit downstream signaling is measured. Its antiviral activity can also be assessed in cell-based assays. These assays demonstrate the compound's functional activity in a relevant cellular context.

Animal/Disease Models: Swiss mice [3]
Doses: 0.01 mL/g
Route of Administration: Antazoline (IP; 0.01 ml/g; 30 minutes)
Experimental Results: Displayed certain proconvulsant activity.
In vivo animal studies for antazoline have been conducted in models of allergic conjunctivitis to evaluate its efficacy. However, specific details of these studies are not extensively detailed in the available literature. Its clinical efficacy has been established in human use for allergic conjunctivitis.

Antazoline is administered topically as eye drops. Its systemic absorption is minimal, which reduces the risk of systemic side effects. Its pharmacokinetic properties are characterized by its local action. When used systemically, it is metabolized in the liver and excreted in urine.

Interactions
This study aimed to investigate the effects of antazoline and ketotifen (two H1 receptor antagonists) on the anticonvulsant activity of antiepileptic drugs induced by maximal electroconvulsive shock (MES) in mice. The antiepileptic drugs used included sodium valproate, carbamazepine, phenytoin sodium, and phenobarbital. Furthermore, the effects of antiepileptic drugs alone or in combination with antazoline or ketotifen on long-term memory (passive avoidance task test) and motor ability (chimney test assessment) in mice were investigated, including the effects during the acute phase and after 7 days of continuous H1 receptor antagonist administration. The effects of antazoline and ketotifen on the plasma and brain tissue free drug concentrations of the antiepileptic drugs were also evaluated. After acute administration and 7 days of treatment, antazoline (0.5 mg/kg) significantly reduced the electroconvulsive shock threshold. Similarly, after acute administration and chronic administration (8 mg/kg), ketotifen also significantly reduced the electroconvulsive shock threshold. At lower doses, neither antazoline nor ketotifen had any effect on this parameter. Atazoline (0.25 mg/kg) significantly increased the ED50 value of carbamazepine for maximal electroconvulsive shock (MES) (both after acute administration and 7 days of treatment). Furthermore, antazoline (0.25 mg/kg) reduced the anticonvulsant activity of phenytoin sodium, but only after repeated administration and without affecting the drug's concentrations in brain tissue and plasma. Moreover, the protective effects of sodium valproate and phenobarbital were not altered when used in combination with antazoline. …Acute administration of antazoline (0.25 mg/kg) in combination with sodium valproate alone impaired performance in mice on the pole climbing test. Ketotifen (4 mg/kg) in combination with conventional antiepileptic drugs impaired motor coordination in mice treated with sodium valproate, phenobarbital, or phenytoin sodium. Acute or chronic administration of antazoline (0.25 mg/kg) alone or in combination with antiepileptic drugs did not interfere with long-term memory in the passive avoidance task test. ...These results indicate that H1 receptor antagonists can cross the blood-brain barrier and should therefore be used with caution in patients with epilepsy. This is because antazoline reduces the protective effects of phenytoin sodium and carbamazepine. Imidazolinones have neuroprotective effects in cerebral ischemia models. They can also counteract N-methyl-D-aspartate (NMDA)-induced neuronal death in the cerebellum and striatum of mice by blocking NMDA currents. This study investigated the effects of antazoline on NMDA toxicity and currents in rat hippocampal neuronal cultures, and its effect on an in vivo status epilepticus model. In hippocampal neuronal cultures, antazoline (30 μM) reduced NMDA-mediated neurotoxicity and blocked NMDA currents in a voltage-dependent and rapidly reversible manner (inhibition rate of 85 ± 3% at -60 mV). Status epilepticus was induced by direct injection of pilocarpine (200 nmol) into the right piriform cortex of adult male rats. Subsequently, rats were immediately given three intraperitoneal injections, 30 minutes apart, of PBS (control group), 10 mg/kg antazoline (low-dose group), or 45 mg/kg antazoline (high-dose group). During the 6-hour recording period, status epilepticus lasted for more than 200 minutes in all groups. Only in the high-dose group did seizures completely cease 1 hour after the third antazoline injection, only to recur 1 hour later. Rats were sacrificed one week later, and their brain tissue was analyzed using cresol purple staining to quantify the degree of damage. On the ipsilateral side of the pilocarpine injection, the piriform cortex and hippocampal CA1 and CA3 regions were significantly protected in the antazoline treatment group, while the anterior piriform cortex and entorhinal cortex were protected only in the high-dose group. On the contralateral side of the pilocarpine injection, only the hippocampal CA3 region was significantly protected in the low-dose group, while all structures examined were protected in the high-dose group. In summary, antazoline is a potent neuroprotective agent used in various primary culture models of neurons, as previously demonstrated in striatal and cerebellar granule neurons, and in hippocampal neurons in this study. Atazoline also exhibits in vivo neuroprotective effects in a pilocarpine-induced status epilepticus model induced by intrapyriform fossa injection.

---

Non-human toxicity values
Mouse LD50 398 mg/kg
Mouse intraperitoneal LD50 100 mg/kg
Mouse subcutaneous LD50 135 mg/kg

Antazoline is generally well-tolerated when used topically. Local adverse effects may include stinging, burning, and blurred vision. Systemic toxicity is rare but can occur with overdose. It is not recommended for use in patients with narrow-angle glaucoma due to its anticholinergic effects. It is available as an over-the-counter or prescription medication.

[1]. Efficacy and safety of antazoline for cardioversion of atrial fibrillation: propensity score matching analysis of a multicenter registry (CANT II Study). Pol Arch Intern Med. 2022 Jun 29;132(6):16234.

[2]. Repurposing of Antazoline Hydrochloride as an Inhibitor of Hepatitis B Virus DNA Secretion. Virol Sin. 2021 Jun;36(3):501-509.

[3]. Influence of antazoline and ketotifen on the anticonvulsant activity of conventional antiepileptics against maximal electroshock in mice. Eur Neuropsychopharmacol. 2004 Aug;14(4):307-18.

Amatazolin belongs to the imidazoline class of compounds. Its chemical name is 2-aminomethyl-2-imidazoline, in which the amino hydrogen atom is replaced by a benzyl group and a phenyl group. Amatazolin is only present in individuals who have taken the drug. It has H1 receptor antagonist, cholinergic antagonist, and xenobiotic effects. It is a tertiary amine compound, an aromatic amine, and a member of the imidazoline class. Amatazolin is a first-generation antihistamine with anticholinergic activity. It is used to relieve nasal congestion. It can also be formulated with naphazoline into eye drops to relieve allergic conjunctivitis. Amatazolin is an ethylenediamine derivative with histamine H1 receptor antagonistic and sedative effects. Amatazolin antagonizes histamine H1 receptors, preventing typical allergic symptoms caused by histamine acting on capillaries, skin, mucous membranes, and gastrointestinal and bronchial smooth muscle. These histamine effects include vasodilation, bronchoconstriction, increased vascular permeability, pain, itching, and gastrointestinal smooth muscle spasms. Astatin is used to relieve allergy symptoms.
Histamine H1 receptor antagonist.
See also: Astatin phosphate; Naphazoline hydrochloride (note moved to).
Indications
For nasal congestion relief, usually used in combination with naphazoline as eye drops to relieve symptoms of allergic conjunctivitis.
Mechanism of Action
Astatin binds to histamine H1 receptors. This blocks the action of endogenous histamine, thereby temporarily relieving histamine-induced adverse symptoms.
Anthistamines are competitive, reversible inhibitors of histamine's action on H1 receptors. /Antihistamines/

---

Therapeutic Uses
Anti-allergy medication; Histamine H1 receptor antagonist
Apatazoline…is an antihistamine used orally and as eye drops…
In two independent studies, each enrolling 25 subjects, naphazoline significantly improved histamine-induced red eye and itching symptoms (but did not relieve itching). In the same model, antazoline significantly suppressed itching (but did not relieve red eye). The combination of naphazoline and antazoline significantly improved red eye symptoms and suppressed itching in all histamine-stimulated eyes. The combination of the two drugs is more effective in preventing red eye than either drug alone. Antihistamines and antihistamine/vasoconstrictor combination preparations are comparable in their effectiveness in relieving itching.
Apatazoline is an ethylenediamine derivative with the characteristics and uses of an antihistamine. It is one of the least active commonly used antihistamines, with a short duration of action. It has local anesthetic effects and also possesses some anticholinergic properties. It is claimed to be less irritating to tissues than most other antihistamines. For more complete data on the therapeutic uses of antazoline (9 in total), please visit the HSDB record page. Other common adverse reactions include dizziness, tinnitus, blurred vision, euphoria, ataxia, anxiety, insomnia, tremor, nausea, vomiting, constipation, diarrhea, upper abdominal discomfort, dry mouth, and cough. Occasionally, urinary retention, palpitations, hypotension, headache, hallucinations, and psychosis may occur. Rarely, leukopenia, agranulocytosis, hemolytic anemia, allergic reactions, arrhythmias, movement disorders, seizures, paresthesia, paralysis, and hepatitis may occur. /Antihistamines/ In therapeutic use, most antihistamines have similar adverse reactions. The most common side effect of sedative antihistamines is central nervous system depression. Its effects range from mild drowsiness to deep sleep, including fatigue, dizziness, and ataxia. Paradoxical excitation may occasionally occur, especially at high doses, in children, or in the elderly. The sedative effect may diminish after a few days of treatment. /Antichrist/

---

Pharmacodynamics
Amatazolin is a histamine H1 receptor antagonist. It selectively binds to histamine H1 receptors without activating them, thereby blocking the effects of endogenous histamine.
Antazoline is a first-generation antihistamine used for the relief of allergic conjunctivitis. It is a histamine H1 receptor antagonist with anticholinergic properties. It is usually used in combination with naphazoline in eye drops. It has antiviral properties. It is available as a topical medication.

C17H19N3

265.35286

265.157

91-75-8

Antazoline hydrochloride;2508-72-7

2200

White to off-white solid powder

1.1±0.1 g/cm3

475.5±38.0 °C at 760 mmHg

159ºC

241.4±26.8 °C

0.0±1.2 mmHg at 25°C

1.608

4.39

1

2

5

20

314

0

C1(CN(C2=CC=CC=C2)CC3=CC=CC=C3)=NCCN1

REYFJDPCWQRWAA-UHFFFAOYSA-N

InChI=1S/C17H19N3/c1-3-7-15(8-4-1)13-20(14-17-18-11-12-19-17)16-9-5-2-6-10-16/h1-10H,11-14H2,(H,18,19)

N-benzyl-N-(4,5-dihydro-1H-imidazol-2-ylmethyl)aniline

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.)