| Size | Price | Stock | Qty |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Corneal esterases (dipivefrin is hydrolyzed to epinephrine by these enzymes) [2]
β-adrenergic receptors (memory-enhancing effects are blocked by propranolol, a β-adrenergic antagonist, suggesting involvement of central β-adrenergic mechanisms) [3] |
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| ln Vitro |
In corneal homogenates from rabbits, the rate of disappearance of esterified epinephrine (dipivefrin plus monopivalepinephrine) at 37°C was measured. In control homogenates, the rate was 66.3 ± 21.7 pmole/mg protein/min; after in vitro addition of echothiopate iodide (0.25%), the rate decreased to 43.8 ± 25.1 pmole/mg protein/min. In homogenates from corneas pretreated in vivo with echothiopate (0.25% ophthalmic solution, three times daily for five days), the rate was 80.8 ± 22.4 pmole/mg protein/min; addition of echothiopate in vitro reduced it to 38.5 ± 17.6 pmole/mg protein/min. The differences were statistically significant. [2]
Lineweaver-Burk analysis of dipivefrin hydrolysis by corneal homogenates showed that in the absence of echothiopate, Vmax was 13.8 pmole/mg/min and Km was 0.26 mM (95% CI for Vmax: 0.67-5.71×10², for slope: 0.41-1.16×10²). In the presence of 0.05% echothiopate iodide, Vmax was 25.2 pmole/mg/min and Km was 0.47 mM (95% CI for Vmax: 0.20-7.73×10², for slope: 1.28-2.43×10²). The overlapping confidence intervals of the y-intercepts (Vmax⁻¹) and non-overlapping intervals of the slopes indicate competitive inhibition. [2] |
| ln Vivo |
Memory enhancement via central beta-adrenergic systems is induced by dipifurine hydrochloride (0.3-10 μg/kg; i.p.); alpha-adrenergic mechanisms are not involved [3].
In a randomized, double-blind, crossover study involving 12 ophthalmologically normal volunteers (aged 20-26 years), a single instillation (35 μl) of dipivefrine 0.1% into one eye produced the following effects: - Pupil diameter measured by infrared pupillometry: significant mydriasis from baseline 5.44 mm (SD 0.79) to 6.19 mm (SD 1.09) at 90 min after instillation (P=0.010). The mean pupil index (area under the response curve divided by time) was 5.71 mm (SD 0.94), which was not significantly different from saline (5.70 mm, SD 0.88) but significantly larger than pilocarpine (2.59 mm, SD 0.57) (ANOVA, P<0.001). No significant changes were observed in the untreated eyes. [1] - Automated perimetry (Humphrey Field Analyzer, program 30-2) performed at baseline and 60 min after instillation: no significant changes in global indices. Mean deviation (MD) changed from -2.49 dB (baseline) to -2.67 dB (T60) (mean difference 0.18 dB, SD 0.45, P<0.20). Pattern standard deviation (PSD) changed from 2.27 dB to 2.24 dB (mean difference 0.03 dB, SD 0.43, P<0.77). Short-term fluctuation (SF) changed from 1.20 dB to 1.39 dB (mean difference 0.19 dB, SD 0.34, P<0.09). No significant changes in PSD² or SF². [1] - Distance visual acuity assessed by high-contrast and low-contrast LogMAR charts at baseline and up to 90 min post-instillation: no significant effect. Mean LogMAR index for high-contrast letters was -0.09 (SD 0.11) and for low-contrast letters 0.07 (SD 0.12). Paired comparison between dipivefrin and pilocarpine showed significant differences (high-contrast P=0.003, low-contrast P=0.002). No changes in untreated eyes. [1] |
| Enzyme Assay |
Corneal homogenates were prepared from untreated rabbits. The homogenate was centrifuged at 12,000 g for 10 minutes. 40 µL of 0.5 mg/mL ¹⁴C-labeled dipivefrin in 0.01 M sodium acetate (pH 4) was added to 1 mL of supernatant. The mixture was divided into 100 µL samples. To half of the samples, 25 µL of 0.25% echothiopate iodide was added; to the other half, 25 µL of phosphate-buffered saline (PBS) was added. Tubes were filled with nitrogen, sealed, and kept at 37°C for 0, 10, 20, 30, or 60 minutes. Reactions were stopped by adding 25 µL of 1 N hydrochloric acid in methanol and placing tubes on ice. After centrifugation at 12,000 g for 10 minutes, 10 µL of each supernatant was streaked onto cellulose thin-layer chromatography (TLC) sheets and chromatographed. The rates of disappearance of dipivefrin plus monopivalepinephrine were calculated. [2]
For Lineweaver-Burk analysis, corneal homogenate from an untreated rabbit was used. Final dipivefrin concentrations were 0.5, 0.1, and 0.05 mg/mL (1.03 mM, 0.21 mM, and 0.10 mM). Reactions were measured in the presence and absence of 0.05% echothiopate iodide. Data from four determinations were used to calculate Vmax and Km by the reciprocal method. [2] |
| Animal Protocol |
Animal/Disease Models: Male 60-day-old CFW mice (23-28 g) [3]
Doses: 0.3 μg/kg, 1.0 μg/kg, 3.0 μg/kg, 10 μg/kg Route of Administration: intraperitoneal (ip) injection; results after training Experimental Results: Dramatically enhances retention of inhibitory avoidance and Y-maze discrimination tasks in a dose-dependent manner. In vivo metabolism study in rabbits: Dutch belted rabbits received 1 drop of 0.25% echothiopate iodide ophthalmic solution in the right eye three times daily for four days. On day 5, the first two treatments were administered, and animals were killed 1.5 hours after the second treatment. A 10 µL drop of 0.2% ¹⁴C-dipivefrin in acetate buffer (pH 4.0) was administered to both eyes at 15, 30, or 60 minutes before sacrifice. Corneas, aqueous humors, and iris-ciliary bodies were removed and rapidly frozen. Control animals received only ¹⁴C-dipivefrin. [2] Memory enhancement study in mice: Male 60-day-old CFW mice (23-28 g) were used. For inhibitory avoidance training, mice were placed in a lighted compartment; when they entered the dark compartment, a footshock (0.5 mA, 60 Hz, 2 s) was delivered. Immediately after training, intraperitoneal injections of dipivefrin (0.3-10.0 μg/kg) or saline (10 mL/kg) were given. Retention was tested 48 hours later by recording step-through latency (maximum 300 s). For Y-maze discrimination training, mice were trained to enter a lit safe alley to avoid footshock (0.35 mA, 60 Hz). Training continued until three consecutive correct entries. Post-training i.p. injections were given, and retention was tested 48 hours later using a reversal paradigm (safe alley switched to dark). Errors on six reversal trials were recorded. For antagonist studies, dipivefrin (10.0 μg/kg) was co-administered with propranolol (2.0 mg/kg), sotalol (2.0 mg/kg), prazosin (3.0 mg/kg), yohimbine (3.0 mg/kg), or phentolamine (3.0 mg/kg) i.p. immediately after training. [3] |
| ADME/Pharmacokinetics |
Dipivefrin is a lipophilic prodrug of epinephrine that is hydrolyzed to the active drug epinephrine by esterases in the cornea. In rabbits, topical application of 0.2% ¹⁴C-dipivefrin resulted in rapid hydrolysis: in corneal extracts, most labeled material appeared as epinephrine and its metabolite metanephrine, with little dipivefrin or monopivalepinephrine remaining as early as 15 minutes after treatment. The amount of radioactive material extracted from tissues of echothiopate-treated animals was similar to controls (cornea: 82.4% ± 4.9%; iris-ciliary body: 96.1% ± 4.5%; aqueous humor: 97.9% ± 2.1%). [2]
Dipivefrin is a lipophilic prodrug that penetrates lipid barriers several hundred-fold faster than epinephrine. When administered systemically (i.p.) in mice, dipivefrin is approximately 10-30 times more potent than epinephrine in enhancing memory, suggesting it readily crosses the blood-brain barrier. [3] |
| Toxicity/Toxicokinetics |
Dipivefrin caused mydriasis (mean increase in pupil diameter 0.75 mm over 90 min), and due to this mydriatic effect, it is contraindicated in closed-angle glaucoma. [1]
- In long-term studies cited within this paper, blurred vision was reported by 2 out of 57 and 5 out of 287 subjects experiencing significantly blurred vision. [1] |
| References |
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| Additional Infomation |
Dipiformin hydrochloride is the hydrochloride salt of dipiformin. It is used topically as eye drops to treat open-angle glaucoma or ocular hypertension to lower intraocular pressure. It has the effects of an adrenergic agonist, sympathomimetic agent, and antiglaucoma agent. It contains a dipiformin (1+) molecule. Dipiformin hydrochloride is an ester compound with sympathomimetic activity. Dipiformin hydrochloride is a prodrug of adrenaline and, due to its higher lipophilicity, penetrates more easily into the anterior chamber. Once inside the eye, dipiformin hydrochloride is hydrolyzed to epinephrine. Epinephrine promotes aqueous humor outflow and reduces aqueous humor production through vasoconstriction, thereby lowering intraocular pressure.
Dipivefrin is a prodrug of epinephrine. [1] - It is used in the medical management of open-angle glaucoma as an alternative to, or concomitant with, beta-adrenoceptor blockade. Although no longer a first-line agent, it is still used. [1] - The mydriatic effect of dipivefrin has been reported in several long-term clinical trials involving patients with glaucoma and/or ocular hypertension. In a single-dose study in ocular hypertensives, mydriasis was maximal at 2 h with a mean change of 1.6 mm (SD 1.0). In a long-term study, the mydriatic effect (mean 0.65 mm) was comparable to that of epinephrine 2%. [1] |
| Molecular Formula |
C19H30CLNO5
|
|---|---|
| Molecular Weight |
387.9
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| Exact Mass |
387.181
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| CAS # |
64019-93-8
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| Related CAS # |
Dipivefrin;52365-63-6;Dipivefrin-d6 hydrochloride
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| PubChem CID |
71486
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| Appearance |
White to off-white solid powder
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| Boiling Point |
473.7ºC at 760 mmHg
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| Melting Point |
158-159°
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| Flash Point |
240.3ºC
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| LogP |
4.035
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
26
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| Complexity |
463
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)(C)C(=O)OC1=C(C=C(C=C1)C(CNC)O)OC(=O)C(C)(C)C.Cl
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| InChi Key |
VKFAUCPBMAGVRG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H29NO5.ClH/c1-18(2,3)16(22)24-14-9-8-12(13(21)11-20-7)10-15(14)25-17(23)19(4,5)6/h8-10,13,20-21H,11H2,1-7H31H
|
| Chemical Name |
(1)-4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-phenylene dipivalate hydrochloride
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| Synonyms |
Dipivefrin hydrochloride
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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) |
DMSO : ~250 mg/mL (~644.50 mM)
H2O : ≥ 100 mg/mL (~257.80 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.36 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 20.8 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: ≥ 2.08 mg/mL (5.36 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 20.8 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: ≥ 2.08 mg/mL (5.36 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 | 2.5780 mL | 12.8899 mL | 25.7798 mL | |
| 5 mM | 0.5156 mL | 2.5780 mL | 5.1560 mL | |
| 10 mM | 0.2578 mL | 1.2890 mL | 2.5780 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00459303 | COMPLETEDWITH RESULTS | Device: aspherical intraocular lens Device: spherical intraocular lens |
Cataract | National Taiwan University Hospital | 2005-10 | Phase 4 |
| NCT03049163 | UNKNOWN STATUS | Drug: vitrectomy under topical anesthesia [Proparacaine HCL (Alcaine®)] |
Perioperative Pain Experiences | Lin Zhong | 2016-10 | Not Applicable |
| NCT03049163 | UNKNOWN STATUS | Drug: vitrectomy under topical anesthesia [Proparacaine HCL (Alcaine®)] |
Perioperative Pain Experiences | Lin Zhong | 2016-10 | Not Applicable |
| NCT02251613 | COMPLETEDWITH RESULTS | Drug: Olopatadine HCl ophthalmic solution, 0.1% Drug: Epinastine HCl ophthalmic solution, 0.05% |
Allergic Conjunctivitis | Alcon Research | 2013-12 | Phase 4 |
| NCT02322216 | COMPLETEDWITH RESULTS | Drug: Olopatadine Hydrochloride Ophthalmic Solution 0.2% Drug: Olopatadine Hydrochloride Ophthalmic Solution 0.1% Drug: Olopatadine 0.2% Vehicle |
Allergic Conjunctivitis | Alcon Research | 2014-12 | Phase 3 |
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