Tropicamide

Absorption

Following ocular administration of 40 μL drops of 0.5% tropicamide in female subjects, tropicamide reached its mean peak concentration in plasma of 2.8 ± 1.7 ng/mL (mean ± SD) at five minutes.

Toxicity

Oral LD50 is 865 mg/kg in rats and 565 mg/kg in mice. Intraperitoneal LD50 is 1210 mg/kg in rats and 695 mg/kg in mice. Subcutaneous LD50 is 872 mg/kg in rats and 665 mg/kg in mice.
There is limited information on tropicamide overdose. Systemic adverse effects, such as tachycardia, central nervous system disturbances, and muscle rigidity have been reported with the use of tropicamide. Psychotic reactions, behavioral disturbances, and vasomotor or cardio-respiratory collapse have been reported with the use of anticholinergic in children.

Chemical properties

Crystalline Solid

Originator

Mydriacyl,Alcon,US,1959

The Uses of Tropicamide

Tropicamide, like cyclopentolate, is used in ophthalmoscopy for reaching pre-operational mydraises and for testing narrow-angle glaucoma.

The Uses of Tropicamide

Ophthalmic anticholinergic. Mydriatic

The Uses of Tropicamide

antidepressant, nutrient; LD50(rat) 1634 mg/kg ip

The Uses of Tropicamide

Indicated to induce mydriasis (dilation of the pupil) and cycloplegia (paralysis of the ciliary muscle of the eye) in diagnostic procedures, such as measurement of refractive errors and examination of the fundus of the eye.

Indications

Tropicamide is indicated to induce mydriasis (dilation of the pupil) for diagnostic procedures and in conditions where short-term pupil dilation is desired, either as monotherapy or in combination with hydroxyamphetamine or phenylephrine. It provides clinically significant mydriasis with partial cycloplegia.

Background

Tropicamide is an alkaloid atropine‐derived anticholinergic drug and a non‐selective antagonist of muscarinic acetylcholine (mACh) receptors. Usually available in ophthalmic formulations, tropicamide is used to cause mydriasis and cycloplegia for eye exams or ocular procedures. It is also used in combination with hydroxyamphetamine for the same indication. Oral tropicamide has been investigated as a potential drug to relieve sialorrhea in patients with Parkinson's Disease.

What are the applications of Application

Tropicamide is a mAChR M4 antagonist

Definition

ChEBI: Tropicamide is a member of acetamides.

Manufacturing Process

A solution of 82 parts by weight of γ-chloromethyl-pyridine-hydrochloride in 60 parts of water is added dropwise, at 0° to 5°C, to 250 parts by weight of a 50% aqueous ethyl amine solution. The mixture is stirred for 1 hour at 60°C, whereupon it is cooled down and separated in the cold with solid potassium hydroxide. The oil formed is separated off, dried over potassium hydroxide and distilled. The ethyl-(γ-picolyl)-amine formed boils over at 103° to 104°C under a pressure of 13 mm Hg. Its dihydrochloride melts at 198° to 200°C. To a mixture of 48.7 parts by weight of ethyl-(γ-picolyl)-amine and 36 parts by weight of dry pyridine in 220 parts by weight of dry chloroform is slowly added, while stirring and cooling with ice water, crude acetyltropic acid chloride prepared from 60 parts by weight of tropic acid. To complete the reaction, the mixture is stirred for one additional hour at 23°C. Thereupon the chloroform solution is diluted with 200 parts by weight of ether and agitated with 3 N hydrochloric acid. The weakly Congo acid solution is heated for 1 hour in a steam bath, the acetyl group of the reaction product being thereby split off, and the mixture is filtered over charcoal.
Upon adding concentrated ammonia in excess, the condensation product separates and is taken up in chloroform. The chloroform solution is dried and distilled, the tropic acid N-ethyl-N-(γ-picolyl)-amide being thereby obtained in the form of a thick oil, which crystallizes after prolonged time and which then melts at 96° to 97°C.

brand name

Mydriacyl (Alcon); Tropicacyl (Akorn).

Therapeutic Function

Anticholinergic (ophthalmic)

General Description

Tropicamide, N-ethyl-2-phenyl-N-(4-pyridylmethyl)hydracrylamide (Mydriacyl), is aneffective anticholinergic for ophthalmic use when mydriasisis produced by relaxation of the sphincter muscle ofthe iris, allowing adrenergic innervation of the radial muscleto dilate the pupil. Its maximum effect is achieved inabout 20 to 25 minutes and lasts for about 20 minutes,with complete recovery in about 6 hours. Its action ismore rapid in onset and wears off more rapidly thanthat of most other mydriatics. To achieve mydriasis, either0.5% or 1.0% concentration may be used, althoughcycloplegia is achieved only with the stronger solution.Its uses are much the same as those described above formydriatics in general, but opinions differ on whether thedrug is as effective as homatropine, for example, inachieving cycloplegia. For mydriatic use, however, in examinationof the fundus and treatment of acute iritis,iridocyclitis, and keratitis, it is quite adequate; and becauseof its shorter duration of action, it is less prone toinitiate a rise in intraocular pressure than the more potent,longer-lasting drugs. As with other mydriatics, however,pupil dilation can lead to increased intraocular pressure.In common with other mydriatics, it is contraindicated inpatients with glaucoma, either known or suspected, andshould not be used in the presence of a shallow anteriorchamber. Thus far, no allergic reactions or ocular damagehas been observed with this drug. The ability to clone thevarious muscarinic receptor subtypes has allowed the observationthat tropicamide has modest selectivity for theM4 receptor.

Biological Activity

M 4 selective muscarinic receptor antagonist.

Biochem/physiol Actions

M4 muscarinic acetylcholine receptor antagonist.

Pharmacokinetics

Tropicamide is an anticholinergic drug and that works by non‐selectively blocking muscarinic receptors to cause mydriasis and cycloplegia. It relaxes the pupillary sphincter to dilate the pupil. The onset of tropicamide‐induced mydriasis is about 10 to 15 minutes, with optimal effect occurring 25 to 30 minutes post-administration. Mydriasis caused by tropicamide wears off within four to eight hours, but it was seen up to 24 hours in some individuals. Tropicamide hinders accommodation by causing the contraction of the ciliary muscle. The cycloplegic effect occurs within 20 to minutes following administration, with a duration of action of four to 10 hours. Tropicamide can elevate intraocular pressure. The ophthalmic use of tropicamide is not typically associated with serious systemic adverse events.
One randomized pilot study showed that oral tropicamide alleviated perceived symptoms of sialorrhea in patients with Parkinson's Disease: anticholinergics are believed to restore the dopaminergic to cholinergic activity imbalance in neurodegenerative diseases. Similarly in one case report, tropicamide administered via ophthalmic solution relieved clozapine-induced sialorrhea. Interestingly, in rodent models, tropicamide suppressed drug-induced tremulous jaw movements which are often used as a model of parkinsonian tremor: the significance of this finding requires further investigations.

Synthesis

Tropicamide, N-(4-piridinylmethyl)-N-ethyl-|?-hydroxy-|á-phenylpropionamide (14.1.41), is synthesized by reacting O-acetyltropyl chloride with ethyl (4-piridinylmethyl)amine and the subsequent acidic hydrolysis of the acetyl group in the resulting amide (14.1.40) [31].

Veterinary Drugs and Treatments

Tropicamide, like atropine, causes mydriasis and cycloplegia, but has more mydriatic than cycloplegic activity. Tropicamide has a more rapid onset (maximum mydriasis in 15 – 30 minutes) of action and a shorter duration of action (pupil returns to normal in 6 – 12 hours in most animals) than does atropine, thereby making it more useful for funduscopic examinations. In dogs, intraocular pressure is apparently not affected by tropicamide. Tropicamide is also indicated following cataract removal to prevent synechiae formation that is associated with post-cataract atropine administration. As the half-life of tropicamide is shorter than that of atropine, this allows iris contraction preventing synechial adhesions.

Metabolism

No information can be found.

storage

Store at RT