アンタゾリン

/SIGNS AND SYMPTOMS/ In human eyes 0.75% solution between pH 5 and pH 8 was about the maximum suitable for clinical use. Oral administration of 400 mg antazoline hydrochloride per day for five days to patients with normal eyes caused no change in intraocular pressure or tonographic measurements. /Antazoline hydrochloride/

/SIGNS AND SYMPTOMS/ Allergic thrombocytopenic purpura and agranulocytosis have been reported. Transient dizziness and anorexia have followed the intravenous administration of antazoline, and cardiac arrest has occurred.

/SIGNS AND SYMPTOMS/ A report of interstitial pneumonitis, with fever, rash, and dyspnea, after antazoline; the condition recurred after challenge.

/CASE REPORTS/ Antazoline (Antistina) induced thrombocytopenic purpura occurring on three occasions in a 21 year old woman is reported. After withdrawal of the drug therapy the patient recovered promptly. In vitro investigation demonstrated the presence of an antibody in serum, which in association with antazoline caused complement fixation when added to test platelets. Also platelet agglutinins could be detected in the patient's serum when antazoline was added. The reactions were drug specific and they could still be demonstrated 9 months after the last exposure to the drug.

For more Human Toxicity Excerpts (Complete) data for ANTAZOLINE (6 total), please visit the HSDB record page.

/LABORATORY ANIMALS: Acute Exposure/ On rabbit eyes 1.5% solution of antazoline hydrochloride was the maximum concentraton that could be applied without causing keratitis epithelialis. /Antazoline hydrochloride/

/LABORATORY ANIMALS: Acute Exposure/ Mepyramine (Pyrilamine) and antazoline applied as 2.5% solutions to eyes of rabbits have caused rapid clouding the corneal epithelium, local anesthesia and transitory swelling of the cornea, with recovery in a few days. For a series of anthistaminics, concentrations which might be considered maximum suitable for topical ophthalmic use range from 0.5% to 1%.

/ALTERNATIVE and IN VITRO TESTS/ Imidazolines exert neuroprotection against hypoxia and NMDA toxicity in cerebellar and striatal neuronal cultures, through a voltage-dependent blockade of glutamatergic NMDA receptors. In striatal neuronal cultures from mouse embryos the imidazoline compound, antazoline, inhibits voltage-gated Ca2+ channels by acting at a phencyclidine-like site. This effect was fast, fully reversible, voltage-dependent and predominant on P/Q- and N-type Ca2+ channels. Taken together, these results suggest that imidazolines may elicit neuroprotective effects also by decreasing the release of glutamate through inhibition of presynaptic Ca2+ channels.

/OTHER TOXICITY INFORMATION/ In unanesthetized cats micturition produced by thyrotropin releasing hormone was investigated after its injection into the cerebral ventricles through chronically implanted cannulae. Thyrotropin releasing hormone in doses from 0.1 to 1.0 mg evoked dose-dependent micturition. In cats treated with intracerebroventricular reserpine and 6-hydroxydopamine, but not with intracerebroventricular 5,6-dihydroxytryptamine and hemicholinium, the micturition caused by intracerebroventricular thyrotropin releasing hormone was abolished. Chlorpromazine and antazoline injected into the cerebral ventricles prevented the micturition induced by intracerebroventricular thyrotropin releasing hormone. On the other hand, mecamylamine, yohimbine, propranolol, atropine and methysergide injected intracerebroventricular had virtually no effect or partially antagonized the micturition evoked by thyrotropin releasing hormone similarly injected. It is apparent therefore that centrally induced thyrotropin releasing hormone micturition could be related to central catecholaminergic mechanisms.

/OTHER TOXICITY INFORMATION/ The effects were investigated of intracerebroventricular injections in the cat of ganglionic blocking agents, antimuscarinic drugs, alpha and beta adrenergic blocking substances, dopamine antagonists, an antihistamine, reserpine and a 5-hydroxytryptamine antagonist as well as the inhibitors of catecholamines, 5-hydroxytryptamine and acetylcholine synthesis upon convulsions produced by nicotine, which was similarly injected. Mecamylamine and hexamethonium but not atropine, scopolamine, yohimbine, phenoxybenzamine, tolazoline, propranolol, practolol, chlorpromazine, haloperidol, antazoline and methysergide abolished the convulsions evoked by nicotine. Furthermore, reserpine, but not 6-hydroxydopamine, as well as 5,6-dihydroxytryptamine and hemicholinium blocked the convulsions caused by nicotine. It appears, therefore, that the convulsions produced by nicotine are mediated through central nicotinic receptors. However, the depressed catecholaminergic, 5-hydroxytryptaminergic and histaminergic mechanisms induced by reserpine can also suppress the convulsions evoked by nicotine.

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/

Antazoline was reported to be a hemolytic agent in subjects deficient in glucose-6-phosphate dehydrogenase but only in conjunction with other factors such as infection.

Most patients require only symptomatic and supportive care. Treatment is focused on controlling agitation, maintaining airway, reversing hyperthermia, and supporting hemodynamic function. Gastrointestinal decontamination is not essential, but if not more than 1 hours has elapsed since ingestion of the drug, activated charcoal may be considered. In view of the potential cardiac toxicity in addition to maintenance of the airway, breathing, and circulatory status of the patients, observation for dysrhythmia is warranted. Clinical assessment for signs that may indicated impending seizure activity (hypertonicity, hyperreflexia, or myoclonic jerking) is important. ... /Antihistamines/

Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

LD50 Mouse 398 mg/kg

LD50 Mouse ip 100 mg/kg

LD50 Mouse sc 135 mg/kg

Prepared by the condensation of benzylaniline with 2-(chloromethyl)imidazoline.

Synthesis of Ethylenediamines. Three different methods of synthesizing ethylenediamines are widely used: 1. Reaction of tertiary chloroethylamines with secondary amines in the presence of a base, e.g., NaH, NaNH2, NaOC2H5, or KOH. 2. Alkylation of secondary amines, such as N-(2-dimethylaminoethyl)aniline with benzyl chlorides in the presence of a strong base. 3. Reaction of reactive heterocyclic halogen compounds, such as 2-bromopyridine with secondary amines, such as N-(2-dimethylaminoethyl)-aniline, also in the presence of a strong base. /Ethylenediamies/

Oral tablets; 100, 200 mg Arithmin, Lammett.

Antistin-Privine (Ciba, UK). An aqueous iso-osmotic solution containing antazoline 0.5% and naphazoline nitrate 0.025%. For allergic conditions of the nose. /Antazoline sulfate/

Trade names: Ocuclear Eye Drops (Schering), Visine L.R. Eye Drops (Pfizer).