CN110327350B - Application of dopamine D1 receptor antagonist SCH39166 in preparation of drugs for treating pathological angiogenesis of eyes - Google Patents
Application of dopamine D1 receptor antagonist SCH39166 in preparation of drugs for treating pathological angiogenesis of eyes Download PDFInfo
- Publication number
- CN110327350B CN110327350B CN201910622660.6A CN201910622660A CN110327350B CN 110327350 B CN110327350 B CN 110327350B CN 201910622660 A CN201910622660 A CN 201910622660A CN 110327350 B CN110327350 B CN 110327350B
- Authority
- CN
- China
- Prior art keywords
- sch39166
- angiogenesis
- eyes
- dopamine
- receptor antagonist
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Ophthalmology & Optometry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Abstract
The dopamine D1 receptor antagonist SCH39166 is used for preparing a medicine for treating pathological angiogenesis of eyes, can inhibit angiogenesis of eyes, has remarkable effect on angiogenesis of retina, cornea and choroid, and can be used for adjuvant treatment of angiogenesis eye diseases.
Description
Technical Field
The invention particularly relates to the technical field of novel application of SCH39166, and particularly relates to application of a dopamine D1 receptor antagonist SCH39166 in preparation of a medicine for treating pathological angiogenesis of eyes.
Background
Ocular neovascularization includes retinal, corneal and choroidal neovascularization. Retinal neovascularization is common in diabetic retinopathy, retinopathy of prematurity, central retinal vein occlusion, neovascular glaucoma and the like; choroidal neovascularization is common in age-related macular degeneration, pathological myopia, and the like. Angiogenesis is normally in a state of dynamic equilibrium under the regulation of pro-angiogenic and anti-angiogenic factors, but when in an ischemic, hypoxic or inflammatory environment, this equilibrium is broken and angiogenesis is promoted. Pathological angiogenesis in the eye, especially the retinal and choroidal neovascularization mentioned above, can cause various complications in the eye, such as vitreous blood, formation of fibrovascular membranes, tractional retinal detachment, macular hemorrhage, etc., which can cause severe visual loss and even blindness.
Epidemiological investigations have shown that ocular neovascular diseases have become the second leading cause of irreversible blindness next to cataracts worldwide, and their blindness rate is still increasing year by year. However, although the traditional treatment methods such as retinal photocoagulation or condensation can inhibit the generation of new blood vessels to a certain extent, part of vision is damaged, and the effect of the traditional treatment methods is not lasting and needs to be repeated; the anti-VEGF medicine used as the first line at present has a definite curative effect, but also has the problems of short maintenance time, multiple injections and the like. Furthermore, VEGF is not only an angiogenic growth factor but also a neurotrophic factor, and if used excessively, it may cause side effects such as growth or retinal vessel growth retardation, particularly in premature infants.
In prior studies, dopamine systems have been shown to modulate angiogenesis by modulating VEGF expression.
Disclosure of Invention
In order to solve the technical defects in the prior art, the invention provides application of a dopamine D1 receptor antagonist SCH39166 in preparation of a medicine for treating pathological angiogenesis of eyes, and provides a method for inhibiting angiogenesis of eyes by antagonizing dopamine D1 receptors.
The technical solution adopted by the invention is as follows: application of dopamine D1 receptor antagonist SCH39166 in preparation of drugs for treating pathological angiogenesis of eyes.
The pathological angiogenesis of the eye refers to one of retinal angiogenesis, corneal angiogenesis and choroidal angiogenesis.
The medicine comprises a pharmaceutically effective amount of SCH39166 and a pharmaceutically acceptable carrier.
The carrier is selected from common pharmaceutical excipients, normal saline or distilled water.
A medicine for treating pathologic angiogenesis of eye is prepared by adding conventional adjuvants into SCH39166, and making into clinically acceptable mixture, capsule, tablet, film, eye drop, and injection by conventional method.
The invention has the beneficial effects that: the invention provides application of a dopamine D1 receptor antagonist SCH39166 in preparation of a medicine for treating pathological angiogenesis of eyes, which can inhibit angiogenesis of eyes, has a remarkable effect on angiogenesis of retina, cornea and choroid parts, and can assist in treating angiogenesis eye diseases.
Drawings
FIG. 1 shows that intraperitoneal injection of SCH39166 inhibited angiogenesis in oxygen-induced retinal damage.
FIG. 2 shows that SCH39166 was administered topically to inhibit corneal angiogenesis.
FIG. 3 shows that intraperitoneal injection of SCH39166 inhibited laser-induced choroidal angiogenesis.
In the figure, the comparison between the DMSO solvent group and the SCH39166 administration group was performed using independent sample t test: "+" indicates P < 0.05 and "+" indicates P < 0.01.
Detailed Description
SCH39166 inhibition of retinal angiogenesis in oxygen-induced retinal injury
After 5 days of breeding the C57BL/6 mice in the same litter in 75% high oxygen environment, the mice are transferred to normal oxygen environment for further breeding on the P12 days, and the abdominal cavity administration is started from the P12 days until the P17 days for taking materials. In the relatively hypoxic stage SCH39166 drug-treated group, the area of the non-perfused area of the retina was significantly increased (DMSO vs SCH: 13.71% + -2.64% vs 18.73% + -3.56%, P = 0.0111, independent t-test) compared to the solvent DMSO control group, while the area of the pathological neovasculature was significantly reduced (DMSO vs SCH39166: 4.40% + -1.24% vs 2.29% + -0.83%, P = 0.0030, independent t-test) (FIG. 1). It was demonstrated that DRD1 antagonists inhibited pathological neovascularization during the relatively hypoxic phase of the OIR model.
SCH39166 inhibits laser-induced choroidal angiogenesis
The DRD1 antagonist SCH39166 was injected in the abdominal cavity after CNV molding in 8-10 weeks old C57BL/6 mice, which were harvested 7 days after the experiment, and the results showed that laser-induced choroidal neovascularization in the drug-treated group was significantly smaller than that in the DMSO solvent control group, and the size of the CNV in the SCH3166 drug-treated group was only 0.454 + -0.126 (P = 0.0276, independent t-test) of that in the DMSO solvent control group (FIG. 3). The DRD1 antagonist SCH39166 has obvious effect of inhibiting the neovascularization in a mouse CNV model, and the antagonist DRD1 can inhibit the neovascularization of choroidal vessels.
In conclusion, according to the above experiments, it is proved that SCH39166 antagonizes ocular dopamine D1 receptor, can inhibit ocular angiogenesis, has significant effect on neovascularization at retina, cornea and choroid, and can assist in treating angiogenesis ocular diseases.
The skilled person should understand that: although the invention has been described in terms of the above specific embodiments, the inventive concept is not limited thereto and any modification applying the inventive concept is intended to be included within the scope of the patent claims.
The above description is only a preferred embodiment of the present invention, and the protection scope of the present invention is not limited to the above embodiments, and all technical solutions belonging to the idea of the present invention belong to the protection scope of the present invention. It should be noted that modifications and embellishments within the scope of the invention may occur to those skilled in the art without departing from the principle of the invention, and are considered to be within the scope of the invention.
Claims (4)
1. Application of dopamine D1 receptor antagonist SCH39166 in preparation of drugs for treating pathological angiogenesis of eyes.
2. The use according to claim 1, wherein said pathologic ocular angiogenesis is one of retinal, corneal and choroidal neovascularization.
3. The use of claim 1, wherein the medicament comprises a pharmaceutically effective amount of SCH39166 and a pharmaceutically acceptable carrier.
4. The use according to claim 3, wherein the carrier is selected from conventional pharmaceutical excipients, physiological saline or distilled water.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910622660.6A CN110327350B (en) | 2019-07-11 | 2019-07-11 | Application of dopamine D1 receptor antagonist SCH39166 in preparation of drugs for treating pathological angiogenesis of eyes |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910622660.6A CN110327350B (en) | 2019-07-11 | 2019-07-11 | Application of dopamine D1 receptor antagonist SCH39166 in preparation of drugs for treating pathological angiogenesis of eyes |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110327350A CN110327350A (en) | 2019-10-15 |
| CN110327350B true CN110327350B (en) | 2021-02-23 |
Family
ID=68146132
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910622660.6A Active CN110327350B (en) | 2019-07-11 | 2019-07-11 | Application of dopamine D1 receptor antagonist SCH39166 in preparation of drugs for treating pathological angiogenesis of eyes |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110327350B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110833621A (en) * | 2019-12-06 | 2020-02-25 | 中国医科大学 | Application of dopamine receptor 1 antagonist in preparation of drug for treating mouse schizophrenia caused by ketamine |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1283116A (en) * | 1997-10-28 | 2001-02-07 | 先灵公司 | Method of reducing craving in mamals |
-
2019
- 2019-07-11 CN CN201910622660.6A patent/CN110327350B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1283116A (en) * | 1997-10-28 | 2001-02-07 | 先灵公司 | Method of reducing craving in mamals |
Non-Patent Citations (2)
| Title |
|---|
| Bright Light Suppresses Form-Deprivation Myopia Development With Activation of Dopamine D1 Receptor Signaling in the ON Pathway in Retina;Si Chen等;《IOVS》;20170430;第58卷(第4期);第2306–2316页 * |
| 多巴胺与早产儿视网膜病变近视的关系;王小芳等;《中国斜视与小儿眼科杂志》;20161231;第24卷(第2期);第44-45页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110327350A (en) | 2019-10-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2017061467A5 (en) | ||
| TWI629985B (en) | Agent for treating ocular fundus diseases | |
| KR102307421B1 (en) | Multiple kinase inhibitors and use in ocular fibrosis | |
| JP2009511604A (en) | Methods for treating primary and secondary forms of glaucoma | |
| RU2519739C2 (en) | Ophthalmological pharmaceutical compositions for neoangiogenic eye pathologies | |
| US10034885B2 (en) | Corneal thickness modulating agent | |
| EP3808352A1 (en) | Use of salidroside and derivative thereof in preparation of inhibitor medicament for diseases of ophthalmic fibrosis caused by abnormalities of extracellular matrix proteins | |
| KR20200116953A (en) | Medications for the prevention or treatment of ophthalmic diseases accompanying intraocular angiogenesis and/or hyperintraocular vascular permeability | |
| CN110327350B (en) | Application of dopamine D1 receptor antagonist SCH39166 in preparation of drugs for treating pathological angiogenesis of eyes | |
| US11478465B2 (en) | Compounds for treatment of eye diseases associated with excessive vascularisation | |
| JP2024041947A (en) | Intraocular pressure lowering enhancer | |
| CN106999500A (en) | Medicinal treatment for preventing or treating glaucoma | |
| TW201904610A (en) | Non-antibody vegf antagonists for the treatment of neovascular glaucoma | |
| JPWO2005079792A1 (en) | Preventive or therapeutic agent for severe diabetic retinopathy | |
| US20080070855A1 (en) | Treatment with anti-VEGF agents to prevent postoperative inflammation and angiogenesis in normal and diseased eyes | |
| KR20170088875A (en) | Anti-inflammatory and mydriatic intracameral solutions for inhibition of postoperative ocular inflammatory conditions | |
| US20200188405A1 (en) | Composition for treating ocular disorders such as macular degeneration, retinopathy and glaucoma | |
| JP4150846B2 (en) | Retinal choroidal disease treatment containing steroid as active ingredient | |
| Duszak et al. | Drugs used in ocular treatment | |
| CN113082031A (en) | Application of dopamine D1 and D2 receptor nonselective agonist in preparation of drugs for treating pathological angiogenesis of eyes | |
| KR20030087029A (en) | Remedies for retina and choroid diseases containing steroids as the active ingredient | |
| EP2875811A1 (en) | Use of dobesilate for treating ocular haemorrhages | |
| Bandello et al. | New perspectives in the management of post-surgical macular edema | |
| Croasdell | Association for Research in Vision and Ophthalmology (ARVO)-2016 Annual Meeting. Seattle, Washington, USA-April 29-May 5, 2016 | |
| SHARM et al. | Clinical Utilisation of Bevacizumab and Patient Monitoring in Retinal Vein Occlusion and Diabetic Macular Edema |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |