Interactions
The purpose of this study was to investigate the effects of antazoline and ketotifen (two H1 receptor antagonists) on the anticonvulsant activity of antiepileptic drugs against maximal electroshock (MES)-induced convulsions in mice. The following antiepileptic drugs were used: valproate, carbamazepine, diphenylhydantoin and phenobarbital. In addition, the effects of antiepileptic drugs alone or in combination with antazoline or ketotifen were studied on long-term memory (tested in the passive avoidance task) and motor performance (evaluated in the chimney test), acutely and after 7-day treatment with these H1 receptor antagonists. The influence of antazoline and ketotifen on the free plasma and brain levels of the antiepileptics was also evaluated. Antazoline (at 0.5 mg/kg), given acutely and after 7-day treatment, significantly diminished the electroconvulsive threshold. Similarly, ketotifen, after acute and chronic doses of 8 mg/kg markedly reduced the threshold for electroconvulsions. In both cases, antazoline and ketotifen were without effect upon this parameter at lower doses. Antazoline (0.25 mg/kg) significantly raised the ED50 value of carbamazepine against MES (both, acutely and after 7-day treatment). Furthermore antazoline (0.25 mg/kg) also reduced the anticonvulsant activity of diphenylhydantoin, but only after repeated administration, without modifying the brain and free plasma level of this drug. Moreover, valproate and phenobarbital did not change their protective activity when combined with antazoline. ... Only acute antazoline (0.25 mg/kg) applied with valproate impaired the performance of mice evaluated in the chimney test. Ketotifen (4 mg/kg) co-administered with conventional antiepileptic drugs impaired motor coordination in mice treated with valproate, phenobarbital or diphenylhydantoin. Acute and chronic antazoline (0.25 mg/kg) alone or in combination with antiepileptic drugs did not disturb long-term memory, tested in the passive avoidance task. ... The results of this study indicate that H1 receptor antagonists, crossing the blood brain barrier, should be used with caution in epileptic patients. This is because antazoline reduced the protective potential of diphenylhydantoin and carbamazepine.
Imidazoline drugs exert neuroprotective effects in cerebral ischaemia models. They also have effects against mouse cerebellar and striatal neuronal death induced by N-methyl-D-aspartate (NMDA) through the blockade of NMDA currents. Here, we investigated the effects of antazoline on NMDA toxicity and current in rat hippocampal neuronal cultures, and on an in vivo model of status epilepticus. In hippocampal cultures, antazoline (30 uM) decreased NMDA-mediated neurotoxicity and also blocked the NMDA current with voltage-dependent and fast-reversible action (inhibition by 85+ or - 3% at -60 mV). Status epilepticus was induced by injecting pilocarpine (200 nmol) directly into the right pyriform cortex of male adult rats. The rats then received immediately three consecutive i.p. injections at 30-min intervals of either PBS (control group) or antazoline at 10 mg/kg (low-dose group) or at 45 mg/kg (high-dose group). During the 6-hr recording, status epilepticus lasted more than 200 min in all groups. In the high-dose group only, seizures completely ceased 1 hr after the third injection of antazoline, then started again 1 hr later. Rats were killed 1 week later, and Cresyl Violet-stained sections of their brain were analysed for damage quantification. On the ipsilateral side to the pilocarpine injection, pyriform cortex and hippocampal CA1 and CA3 areas were significantly protected in both antazoline-treated groups, whilst prepyriform and entorhinal cortices were only in the high-dose group. On the contralateral side to the pilocarpine injection, only the hippocampal CA3 area was significantly protected in the low-dose group, but all investigated structures were in the high-dose group.In conclusion, antazoline is a potent neuroprotective drug in different models of neuronal primary culture, as previously shown in striatal and cerebellar granule neurons, and here in hippocampal neurons. Antazoline is also neuroprotective in vivo in the intra-pyriform pilocarpine-induced status epilepticus model.

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Non-Human Toxicity Values
LD50 Mouse 398 mg/kg
LD50 Mouse ip 100 mg/kg
LD50 Mouse sc 135 mg/kg

Antazoline is a member of the class of imidazolines that is 2-aminomethyl-2-imidazoline in which the exocyclic amino hydrogens are replaced by benzyl and phenyl groups. Antazoline is only found in individuals that have taken the drug. It has a role as a H1-receptor antagonist, a cholinergic antagonist and a xenobiotic. It is a tertiary amino compound, an aromatic amine and a member of imidazolines.
Antazoline is a 1st generation antihistamine with anticholinergic activity. It is used to relieve nasal congestion. It is also formulated as eye drops with naphazoline to relieve allergic conjunctivitis.
Antazoline is an ethylenediamine derivative with histamine H1 antagonistic and sedative properties. Antazoline antagonizes histamine H1 receptor and prevents the typical allergic symptoms caused by histamine activities on capillaries, skin, mucous membranes, and gastrointestinal and bronchial smooth muscles. These histamine activities include vasodilation, bronchoconstriction, increased vascular permeability, pain, itching, and spasmodic contractions of gastrointestinal smooth muscles. Antazoline is used to provide symptomatic relieve of allergic symptoms.
An antagonist of histamine H1 receptors.
See also: Antazoline phosphate; naphazoline hydrochloride (annotation moved to).

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Drug Indication
Used to relieve nasal congestion and in eye drops, usually in combination with naphazoline, to relieve the symptoms of allergic conjunctivitis.

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Mechanism of Action
Antazoline binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine.
Antihistamine drugs are competitive, reversible inhibitors of the action of histamine at the H1 receptor. /Antihistamines/

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Therapeutic Uses
Anti-Allergic Agents; Histamine H1 Antagonists
Antazoline ... is an antihistamine used orally and also in eyedrops ...
In two independent studies including 25 subjects each, naphazoline caused significant whitening (but did not prevent itching) in the histamine-induced red, itchy eye. Antazoline inhibited itching (but not redness) to a significant degree in the same model. The combination of naphazoline and antazoline produced significant whitening and inhibition of itching in all eyes challenged by histamine. The combination of the two drugs was more effective than either component alone in preventing redness. The antihistamine and combination of antihistamine/vasoconstrictor were equally effective in arresting itching.
Antazoline is an ethylenediamine derivative with the properties and uses of the antihistamines. It is one of the least active of the commonly used antihistamines and has a short duration of action. It has local anaesthetic and also some anticholinergic properties. It is claimed to be less irritating to the tissue than most other antihistamines.
For more Therapeutic Uses (Complete) data for ANTAZOLINE (9 total), please visit the HSDB record page.

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Drug Warnings
Other common adverse reactions include dizziness, tinnitus, blurred vision, euphoria, incoordination, anxiety, insomnia, tremor, nausea, vomiting, constipation, diarrhea, epigastric discomfort, dry mouth, and cough. Infrequently, urinary retention, palpitation, hypotension, headache, hallucination, psychosis, ... may occur. Rarely, leukopenia, agranulocytosis, hemolytic anemia, allergic reactions, dysrhythmias, dyskinesia, seizures, paraesthesia, paralysis, hepatitis, ... are noted../Antihistamines/
In therapeutic use, the adverse effects are similar for most members of the group. The most common side effect of the sedating antihistamines is central nervous system depression. Effects range from slight drowsiness to deep sleep and include lassitude, dizziness, and incoordination. Paradoxic stimulation may occasionally occur, especially at high doses and in children or the elderly. The sedative effects may diminish after a few days of therapeutic use. /Antihistamines/

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Pharmacodynamics
Antazoline is a histamine H1 receptor antagonist. It selectively bind to but does not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine.

C17H20CLN3

301.8138

301.134

2508-72-7

Antazoline;91-75-8

2200

White to off-white solid powder

475.5ºC at 760 mmHg

238 °C

241.4ºC

3.31E-09mmHg at 25°C

3.261

1

2

5

20

314

0

Cl[H].N(C1C([H])=C([H])C([H])=C([H])C=1[H])(C([H])([H])C1C([H])=C([H])C([H])=C([H])C=1[H])C([H])([H])C1=NC([H])([H])C([H])([H])N1[H]

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

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 53 mg/mL (~175.61 mM)

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.)