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]

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]

Absorption, Distribution and Excretion
Following intraocular instillation of 40 μL of 0.5% tropicamide in female subjects, the mean peak plasma concentration of tropicamide reached 2.8 ± 1.7 ng/mL (mean ± standard deviation) at 5 minutes.
No relevant information found.
No relevant information found.
No relevant information found.

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Metabolism/Metabolites
No relevant information found.

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Biological Half-Life
The plasma half-life of tropicamide is 30 minutes.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
There is currently no information regarding the use of tropicamide during lactation. Anticholinergic drugs may interfere with breastfeeding. A single use of ophthalmic tropicamide is unlikely to interfere with breastfeeding; however, with prolonged use, the infant should be observed for signs of reduced milk production (e.g., unsatisfied, poor weight gain). To significantly reduce the amount of medication that enters breast milk after using eye drops, press your finger against the tear duct near the corner of your eye for at least 1 minute, then blot away any excess medication with absorbent paper.
◉ Effects on Breastfed Infants
As of the revision date, no relevant published information was found.
◉ Effects on Lactation and Breast Milk
Anticholinergic drugs may inhibit lactation in animals by suppressing the secretion of growth hormone and oxytocin. Anticholinergic drugs can also lower serum prolactin levels in non-lactating women. Prolactin levels in established lactating mothers may not affect their ability to breastfeed.

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Protein Binding
The degree of protein binding has not been determined. Topiramate binds to albumin.

JOphthalmol.2015;2015:612728;Br J Pharmacol.1993 Dec;110(4):1413-20.

Topiramate belongs to the acetamide class of drugs. Topiramate is an alkaloid derivative of atropine, belonging to the anticholinergic class of drugs, and is also a non-selective antagonist of muscarinic acetylcholine (mACh) receptors. Topiramate is usually available in ophthalmic formulations for mydriasis and cycloplegia to facilitate ophthalmic examinations or surgery. It is also often used in combination with amphetamine for the same indications. Oral topiramate has been investigated as a potential drug to relieve drooling in patients with Parkinson's disease. Topiramate is an anticholinergic drug. The mechanism of action of topiramate is as a cholinergic antagonist. Topiramate is a synthetic muscarinic receptor antagonist that acts similarly to atropine and has anticholinergic properties. After being instilled into the eye, topiramate binds to and blocks the action of muscarinic receptors in the intraocular sphincter and ciliary muscle. This inhibits the response induced by cholinergic stimulation, leading to mydriasis and cycloplegia. Tropicalide is a diagnostic drug, also used to produce transient mydriasis and cycloplegia. Tropicalide is a muscarinic receptor antagonist with pharmacological effects similar to atropine, primarily used as an ophthalmic parasympathetic blocker or mydriatic. See also: Phenylephrine hydrochloride; Tropicalide (component); Hydroxyphenidyl hydrobromide; Tropicalide (component). Indications: Tropicalide is indicated for diagnostic procedures and situations requiring short-term mydriasis, and can be used alone or in combination with hydroxyphenidyl or phenylephrine. It produces clinically significant mydriasis with partial cycloplegia. Mechanism of Action: Muscarinic acetylcholine receptors are involved in various ocular functions. The M₃ subtype is primarily expressed by the smooth muscle cells of the pupillary sphincter (the circular muscle of the iris) and ciliary muscle. Upon exposure to light or the binding of acetylcholine, M3 receptor signaling leads to contraction of the pupillary sphincter and pupillary constriction. The ciliary muscle contracts via M3 receptor signaling, thereby regulating the eye and adapting the lens for near vision. The eye is also innervated by the parasympathetic nervous system: neurons in the ciliary ganglion project to the pupillary sphincter in the ciliary body and iris, controlling accommodation and pupillary constriction. Tropicamide is a non-selective muscarinic receptor antagonist that binds to all subtypes of muscarinic receptors. Tropicamide causes pupillary dilation by relaxing the pupillary sphincter through binding to muscarinic receptors. By blocking muscarinic receptors in the ciliary body, tropicamide also inhibits accommodation. Like other muscarinic receptor antagonists, tropicamide inhibits parasympathetic drive, allowing the sympathetic nervous system to dominate the response. Tropicamide is thought to improve sialorrhea by blocking M4 receptors expressed on the salivary glands and reducing saliva production.

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Pharmacodynamics
Tropicamid is an anticholinergic drug whose mechanism of action is to cause mydriasis and cycloplegia by non-selectively blocking muscarinic receptors. It relaxes the pupillary sphincter, causing pupillary dilation. The onset of mydriasis caused by tropicicamid is approximately 10 to 15 minutes, with the best effect occurring 25 to 30 minutes after administration. The mydriasis effect caused by tropicicamid usually subsides within 4 to 8 hours, but in some individuals it can last up to 24 hours. Tropicicamid inhibits accommodation by causing ciliary muscle contraction. Cycloplegic effect occurs within 20 minutes after administration and lasts for 4 to 10 hours. Tropicicamid can increase intraocular pressure. Ophthalmic tropicicamid usually does not cause serious systemic adverse reactions. A randomized controlled trial showed that oral tropicicamid can relieve drooling in patients with Parkinson's disease: anticholinergic drugs are thought to restore the balance of dopaminergic and cholinergic activity in neurodegenerative diseases. Similarly, in one case report, tropicamide administered as eye drops relieved drooling induced by clozapine. Interestingly, in rodent models, tropicamide inhibited drug-induced tremor of the mandible, a movement often used as a model of tremor in Parkinson's disease: the significance of this finding requires further investigation.

C17H20N2O2

284.35

284.152

1508-75-4

Tropicamide-d3;2673270-13-6

5593

White to off-white solid powder

1.2±0.1 g/cm3

492.8±45.0 °C at 760 mmHg

98 °C

251.8±28.7 °C

0.0±1.3 mmHg at 25°C

1.586

1.15

1

3

6

21

310

0

BGDKAVGWHJFAGW-UHFFFAOYSA-N

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

N-ethyl-3-hydroxy-2-phenyl-N-(pyridin-4-ylmethyl)propanamideInChi Key: BGDKAVGWHJFAGW-UHFFFAOYSA-N

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)

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.

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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.

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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.
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 corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)