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500mg |
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10g |
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Purity: ≥98%
Tropicamide (formerly Ro-17683; Ro 1-7683; trade names Mydral; Mydriafair; Mydriaticum; Mydrum), an approved medication used to dilate the pupil and help with eye examination, is a potent anticholinergic and a muscarinic receptor isoform M4 antagonist with important biological activity. It inhibits M4-muscarinic receptor with an IC50 of 8.0 nM. It is short acting drug for mydriasis and cycloplegia when applied as eye drops.
ln Vitro |
1. We have studied the effects of muscarinic cholinoceptor agonists and specific antagonists on both phasic activity and basal tone of the isolated intravesical ureter of the pig by means of isometric techniques in vitro.
2. Acetylcholine in the presence and absence of physostigmine increased both phasic activity and basal tone of ureteral strips in a concentration-dependent manner. Moreover carbachol, methacholine and oxotremorine-M increased both contractile parameters while bethanechol and McN-A-343 evoked only increases in tone without affecting the frequency of the phasic contractions. 3. The nicotinic receptor blocker, hexamethonium (10(-6)-10(-4) M), failed to modify the contractions evoked by a single dose of carbachol (10(-5) M), whilst the muscarinic antagonist, atropine inhibited both phasic and tonic responses. 4. The muscarinic M1 (pirenzepine), M2 (AF-DX 116 and methoctramine), M3 (4-DAMP, HHSiD and p-F-HHSiD), and putative M4 receptor (tropicamide) antagonists significantly reversed increases in both frequency of phasic activity and baseline tone induced by a submaximal dose of carbachol (10(-5) M). The pIC50 values for inhibition of the induced phasic activity were: atropine (10.16) > 4-DAMP (9.12) > HHSiD (8.22) = methoctramine (7.98) = p-F-HHSiD (7.88 > tropicamide (7.62) = pirenzepine (7.53) = AF-DX 116 (7.45) and for inhibition of basal tone were: atropine (10.73) > 4-DAMP (9.32) > HHSiD (8.65) = pirenzepine (8.43) = p-F-HHSiD (8.38) > methoctramine (7.79) > tropicamide (7.53) > AF-DX 116 (7.04). 5. The antagonist profile indicates that an M, receptor mediates the tonic response while the phasic activity could involve either both M2 and M3 or an M4 muscarinic receptor. These results suggest that different muscarinic receptor subtypes mediate the phasic and tonic contractile activity induced by a submaximal concentration of carbachol in the porcine intravesical ureter. submaximal concentration of carbachol in the porcine intravesical ureter.[2] |
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Enzyme Assay |
The contractile capacity of the preparations was challenged by exposing the preparations to 120 mM potassium-richphysiological saline solution (K+PSS). Induced phasic activity described by frequency (number of contractions
min-') and amplitude (g) of rhythmic contractions and increases in basal tone (g) were examined by single application of increasing concentrations of cholinoceptor agonists such as carbachol, methacholine, oxotremorine-M, bethanechol,acetylcholine and McN-A-343. Carbachol, acetylcholine and
methacholine concentration-response curves were generated in the presence of physostigmine (10-6M) to block acetyl cholinesterase activity. The ureteral strips were stimulated with a single concentration of the muscarinic agonists and potassium-rich Krebs during a period of 3 and 4 min, respec
tively.
Due to the development of a strong tachyphylaxis of the tissue to the agonists, two consecutive concentration-response curves could not be constructed in the same preparation. However, the response to a single submaximal concentration (10-s M) of carbachol was reproducible during repetitive exposures. Therefore, it was used to determine the effect of the muscarinic antagonists: atropine, pirenzepine, methoc tramine, AF-DX 116, 4-DAMP, HHSiD, p-F-HHSiD and tropicamide. First, a control response to carbachol (10-5 M) in absence of antagonist was obtained. The preparations were then incubated with the antagonist for 30 min before carbachol was added. An inhibition curve of single concentrations of antagonist was constructed in a single strip. Control preparations without antagonist incubation were run in parallel to correct for tissue fatigue and time-induced changes.[2] |
ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
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. No information can be found. No information can be found. No information can be found. Metabolism / Metabolites No information can be found. Biological Half-Life Tropicamide has a plasma half-life of 30 minutes. |
Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation No information is available on the use of tropicamide during breastfeeding. Anticholinergic drugs might interfere with breastfeeding. A single dose of ophthalmic tropicamide is not likely to interfere with breastfeeding; however, during long-term use, observe the infant for signs of decreased lactation (e.g., insatiety, poor weight gain). To substantially diminish the amount of drug that reaches the breastmilk after using eye drops, place pressure over the tear duct by the corner of the eye for 1 minute or more, then remove the excess solution with an absorbent tissue. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Anticholinergics can inhibit lactation in animals, apparently by inhibiting growth hormone and oxytocin secretion. Anticholinergic drugs can also reduce serum prolactin in nonnursing women. The prolactin level in a mother with established lactation may not affect her ability to breastfeed. Protein Binding The extent of protein binding has not been established. Tropicamide binds to albumin. |
References |
JOphthalmol.2015;2015:612728;Br J Pharmacol.1993 Dec;110(4):1413-20.
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Additional Infomation |
Tropicamide is a member of acetamides.
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. Tropicamide is an Anticholinergic. The mechanism of action of tropicamide is as a Cholinergic Antagonist. Tropicamide is a synthetic muscarinic antagonist with actions similar to atropine and with an anticholinergic property. Upon ocular administration, tropicamide binds to and blocks the muscarinic receptors in the sphincter and ciliary muscle in the eye. This inhibits the responses from cholinergic stimulation, producing dilation of the pupil and paralysis of the ciliary muscle. Tropicamide is a diagnostic agent and is used to produce short-duration mydriasis and cycloplegia. One of the MUSCARINIC ANTAGONISTS with pharmacologic action similar to ATROPINE and used mainly as an ophthalmic parasympatholytic or mydriatic. See also: Phenylephrine Hydrochloride; Tropicamide (component of); Hydroxyamphetamine hydrobromide; Tropicamide (component of). Drug Indication 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. Mechanism of Action Muscarinic acetylcholine receptors are involved in numerous ocular functions. The M3 subtype is predominantly expressed by smooth muscle cells of the sphincter pupillae, which is a circular muscle of the iris, and ciliary muscles. In response to light or binding of acetylcholine, M3 receptor signalling leads to contraction of the sphincter pupillae and pupil constriction. Contraction of the ciliary muscle via M3 receptor signalling also leads to accommodation, adjusting the lens for near vision. The eye is also innervated by parasympathetic nerves: ciliary ganglion neurons project to the ciliary body and the sphincter pupillae muscle of the iris to control ocular accommodation and pupil constriction. Tropicamide is a non-selective muscarinic antagonist that binds to all subtypes of muscarinic receptors. By binding to muscarinic receptors, tropicamide relaxes the pupillary sphincter muscle and causes pupil dilation. By blocking the muscarinic receptors of the ciliary body, tropicamide also prevents accommodation. Like other muscarinic antagonists, tropicamide inhibits the parasympathetic drive, allowing the sympathetic nervous system responses to dominate. Tropicamide is thought to ameliorate sialorrhea by blocking M4 receptors expressed on salivary glands and reducing hypersalivation. Pharmacodynamics 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. |
Molecular Formula |
C17H20N2O2
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Molecular Weight |
284.35
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Exact Mass |
284.152
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CAS # |
1508-75-4
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Related CAS # |
Tropicamide-d3;2673270-13-6
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PubChem CID |
5593
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Appearance |
White to off-white solid powder
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Density |
1.2±0.1 g/cm3
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Boiling Point |
492.8±45.0 °C at 760 mmHg
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Melting Point |
98 °C
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Flash Point |
251.8±28.7 °C
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Vapour Pressure |
0.0±1.3 mmHg at 25°C
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Index of Refraction |
1.586
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LogP |
1.15
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Hydrogen Bond Donor Count |
1
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Hydrogen Bond Acceptor Count |
3
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Rotatable Bond Count |
6
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Heavy Atom Count |
21
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Complexity |
310
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Defined Atom Stereocenter Count |
0
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InChi Key |
BGDKAVGWHJFAGW-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C17H20N2O2/c1-2-19(12-14-8-10-18-11-9-14)17(21)16(13-20)15-6-4-3-5-7-15/h3-11,16,20H,2,12-13H2,1H3
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Chemical Name |
N-ethyl-3-hydroxy-2-phenyl-N-(pyridin-4-ylmethyl)propanamideInChi Key: BGDKAVGWHJFAGW-UHFFFAOYSA-N
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Synonyms |
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.79 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (8.79 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (8.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 3.5168 mL | 17.5840 mL | 35.1679 mL | |
5 mM | 0.7034 mL | 3.5168 mL | 7.0336 mL | |
10 mM | 0.3517 mL | 1.7584 mL | 3.5168 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Efficacy and safety assessment of intracameral T2380
CTID: null
Phase: Phase 2   Status: Ongoing, Completed
Date: 2008-07-24