WO1995013812A1 - Use of substituted 1,4-dihydropyridine to reduce intraocular pressure - Google Patents
Use of substituted 1,4-dihydropyridine to reduce intraocular pressure Download PDFInfo
- Publication number
- WO1995013812A1 WO1995013812A1 PCT/EP1994/003757 EP9403757W WO9513812A1 WO 1995013812 A1 WO1995013812 A1 WO 1995013812A1 EP 9403757 W EP9403757 W EP 9403757W WO 9513812 A1 WO9513812 A1 WO 9513812A1
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- WIPO (PCT)
- Prior art keywords
- dimethyl
- phenyl
- dihydropyridine
- dimethoxycarbonyl
- nitroxyethoxy
- 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.)
- Ceased
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
Definitions
- the invention relates to the new use of substituted 1,4-dihydropyridines for the production of medicaments for the treatment of eye diseases.
- the invention relates to the use of compounds of the formula I.
- Rl is 1-4C-alkyl
- R2 is 1-4C-alkyl or the radical -CH 2 -S-CH 2 CH 2 - H 2 ,
- R3 means 1-4C-alkyl
- R4 denotes 1-4C-alkyl or a menthyl radical
- R5 and R6 are the same or different and are hydrogen (H), 1-4C-alkyl, 1-4C-alkoxy, cyano (CN), nitro (NQ ? ) Or halogen, X 0, NH, CO, 0 (CH 2 ) Represents -CO or S, Y represents 0, N, NH, S, CO, CONH, COO or a bond line with which
- Y is not 0, NH or S when X is NH
- - Y does not mean CO, COO or CONH when X represents CO
- Y is not N, NH, CONH or COO when X is 0,
- a l-15C-alkylene, 5-7C-cycloalkylene, di-1-4C-alkylene-5-7C-cycloalkane or a group of the formula [(CH 2 ) 2 0] (CH 2 ) 2 with q 1 or 2 means m denotes 1 or (if Y represents N) 2 represents Z represents 0 or NH and p represents a number from 1 to 6, and their pharmacologically acceptable salts for the production of medicaments for the treatment of the pathologically increased intraocular pressure.
- 1-4C-A1kyl stands for straight-chain or branched alkyl radicals with 1 to 4 carbon atoms. Examples include butyl, iso-butyl, sec-butyl, tert. -Butyl -, propyl, isopropyl, ethyl and especially the methyl radical.
- 1-4C-alkoxy radicals contain one of the 1-4C-alkyl radicals mentioned above.
- the methoxy radical is preferred.
- Halogen in the sense of the present invention is bromine, chlorine and fluorine.
- 2-15C-Alkylene stands for straight-chain or branched alkylene radicals with 2 to 15 carbon atoms. Examples are ethylene (-CH 2 CH 2 -), trimethylene (-CH 2 CH 2 CH 2 -), tetramethylene (-CH 2 CH 2 CH 2 CH 2 -), pentamethylene (-CH 2 CH 2 CH 2 CH 2 CH 2 -), hexamethylene (-CH 2 - (CH 2 ) 4 -CH 2 -), octamethylene (-CH 2 - (CH 2 ) 6 -CH 2 -), decamethylene (-CH 2 - (CH 2 ) 8 -CH 2 -), tetradecamethylene (-CH 2 - (CH 2 ) 12 -CH 2 -), 1,2-dimethylethylene [-CH (CH 3 ) -CH (CH 3 ) -], 1,1-dimethyl - ethylene [-C (CH 3 ) 2 -CH 2 -], isopropyl idene [-C
- 5-7C-Cycloalkylene stands for cycloalkylene radicals with 5 to 7 carbon atoms. Cyclohexylene radicals are preferred, the 1,2- and 1,4-cyclohexylene radicals being mentioned, for example.
- Di-1-4C-alkylene-5-7C-cycloalkane stands for cyclic hydrocarbons with 5 to 7 carbon atoms which are substituted by two (identical or different) alkylene residues with 1 to 4 carbon atoms.
- a preferred di-1-4C-alkylene-5-7C-cycloalkane radical is the 1,4-dimethylenecyclohexane radical.
- Suitable pharmacologically acceptable salts for compounds of the formula I are preferably all acid addition salts with inorganic and organic acids commonly used in galenics. Suitable as such are water-soluble and water-insoluble acid addition salts with acids such as, for example, hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, acetic acid, citric acid, D-gluconic acid, benzoic acid, 2- (4-hydroxybenzoyl) benzoic acid, butyric acid, sulfosalicylic acid, maleic acid, maleic acid Lauric acid, malic acid, fumaric acid, succinic acid, oxalic acid, tartaric acid, embonic acid, stearic acid, toluenesulfonic acid, methanesulfonic acid or 3-hydroxy-2-naphthoic acid, the acids in the salt production - depending on whether it is a mono- or polybasic acid and, depending on which salt is desired - be
- the compounds of the formula I are used in particular in the form of those medicaments as are suitable for the treatment of eye diseases.
- suitable pharmaceutical formulations include, for example, emulsions, suspensions, ointments or solutions (e.g. eye drops) in which the amount of hydrogen is advantageously between 0.01 and 99%.
- auxiliaries which are suitable for the desired pharmaceutical formulations on the basis of his specialist knowledge.
- antioxidants for example, to use antioxidants, dispersants, emulsifiers, preservatives, solubilizers or permeation promoters.
- Compounds of the formula I which can be used according to the invention are mentioned in the claims. Particularly noteworthy here are those compounds that have only a low cardiac and / or circulatory activity systemically.
- the compounds of formula I are known from WO92 / 02503.
- the reduction in intraocular pressure in female New Zealand albino rabbits was determined using conventional methods.
- the substances to be examined were dropped in 0.05% solution (50 ⁇ l) into one eye, while a solution of the control substance was dropped into the other eye.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Verwendung substituierter l,4-Dihydropyrid1ne zur Senkung des Augeninnen¬ druckesUse of substituted 1,4-dihydropyridones to lower the intraocular pressure
Anwendungsgebiet der ErfindungField of application of the invention
Die Erfindung betrifft die neue Verwendung von substituierten 1,4-Dihydro- pyridinen zur Herstellung von Arzneimitteln für die Behandlung von Augener¬ krankungen.The invention relates to the new use of substituted 1,4-dihydropyridines for the production of medicaments for the treatment of eye diseases.
Bekannter technischer HintergrundKnown technical background
In der internationalen Patentanmeldung WO92/02503 werden Nitratester be¬ schrieben, die zur Behandlung cardiovaskulärer Erkrankungen eingesetzt wer¬ den sollen. - J.A. Nathanson [Journal of Pharmacology and Experi ental The- rapeutics 260, 956 (1992)] beschreibt die topische Anwendung von Nitrovaso- dilatoren (wie Nitroglyzerin oder Isosorbiddinitrat) am Auge zur Verringe¬ rung des Augeninnendruckes.International patent application WO92 / 02503 describes nitrate esters which are to be used for the treatment of cardiovascular diseases. - YES. Nathanson [Journal of Pharmacology and Experiments Therapy 260, 956 (1992)] describes the topical application of nitrovasodilators (such as nitroglycerin or isosorbide dinitrate) to the eye to reduce the intraocular pressure.
Beschreibung der ErfindungDescription of the invention
Es wurde nun gefunden, daß die unten näher beschriebenen, aus der W092/02503 bekannten Verbindungen für die Behandlung des (krankhaft erhöh¬ ten) Augeninnendruckes in hervorragender Weise geeignet sind.It has now been found that the compounds described in more detail below, known from WO92 / 02503, are outstandingly suitable for the treatment of the (pathologically elevated) intraocular pressure.
Gegenstand der Erfindung ist die Verwendung von Verbindungen der Formel IThe invention relates to the use of compounds of the formula I.
(siehe beiliegendes Formelblatt), worin(see enclosed formula sheet), where
Rl 1-4C-Alkyl bedeutet,Rl is 1-4C-alkyl,
R2 1-4C-Alkyl oder den Rest -CH2-S-CH2CH2- H2 bedeutet,R2 is 1-4C-alkyl or the radical -CH 2 -S-CH 2 CH 2 - H 2 ,
R3 1-4C-Alkyl bedeutet,R3 means 1-4C-alkyl,
R4 1-4C-Alkyl oder einen Menthylrest bedeutet,R4 denotes 1-4C-alkyl or a menthyl radical,
R5 und R6 gleich oder verschieden sind und Wasserstoff (H), 1-4C-Alkyl, l-4C-Alkoxy, Cyan (CN), Nitro (NQ?) oder Halogen bedeuten, X 0, NH, CO, 0(CH2) -CO oder S darstellt, Y 0, N, NH, S, CO, CONH, COO oder einen Bindungsstrich darstellt, mit derR5 and R6 are the same or different and are hydrogen (H), 1-4C-alkyl, 1-4C-alkoxy, cyano (CN), nitro (NQ ? ) Or halogen, X 0, NH, CO, 0 (CH 2 ) Represents -CO or S, Y represents 0, N, NH, S, CO, CONH, COO or a bond line with which
Einschränkung, daß - X und Y nicht gleichzeitig 0 und/oder S bedeuten,Restriction that - X and Y do not simultaneously mean 0 and / or S,
- Y nicht 0, NH oder S bedeutet, wenn X NH darstellt,Y is not 0, NH or S when X is NH,
- Y nicht CO, COO oder CONH bedeutet, wenn X CO darstellt, und- Y does not mean CO, COO or CONH when X represents CO, and
- Y nicht N, NH, CONH oder COO bedeutet, wenn X 0 darstellt,Y is not N, NH, CONH or COO when X is 0,
A l-15C-Alkylen, 5-7C-Cycloalkylen, Di-l-4C-alkylen-5-7C-cycloalkan oder eine Gruppe der Formel [(CH2)20] (CH2)2 mit q = 1 oder 2 bedeutet, m 1 oder (wenn Y N darstellt) 2 bedeutet, Z 0 oder NH darstellt und p eine Zahl von 1 bis 6 bedeutet, und ihren phar akologisch verträglichen Salzen zur Herstellung von Arznei¬ mitteln für die Behandlung des krankhaft erhöhten Augeninnendruckes.A l-15C-alkylene, 5-7C-cycloalkylene, di-1-4C-alkylene-5-7C-cycloalkane or a group of the formula [(CH 2 ) 2 0] (CH 2 ) 2 with q = 1 or 2 means m denotes 1 or (if Y represents N) 2 represents Z represents 0 or NH and p represents a number from 1 to 6, and their pharmacologically acceptable salts for the production of medicaments for the treatment of the pathologically increased intraocular pressure.
1-4C-A1kyl steht für geradkettige oder verzweigte Alkylreste mit 1 bis 4 Kohlenstoffatomen. Beispielsweise seien genannt der Butyl-, iso-Butyl-, sec.-Butyl-, tert. -Butyl -, Propyl-, Isopropyl-, Ethyl- und insbesondere der Methylrest.1-4C-A1kyl stands for straight-chain or branched alkyl radicals with 1 to 4 carbon atoms. Examples include butyl, iso-butyl, sec-butyl, tert. -Butyl -, propyl, isopropyl, ethyl and especially the methyl radical.
l-4C-Alkoxyreste enthalten neben dem Sauerstoffatom einen der vorstehend genannten 1-4C-Alkylreste. Bevorzugt ist der Methoxyrest.In addition to the oxygen atom, 1-4C-alkoxy radicals contain one of the 1-4C-alkyl radicals mentioned above. The methoxy radical is preferred.
Halogen im Sinne der vorliegenden Erfindung ist Brom, Chlor und Fluor.Halogen in the sense of the present invention is bromine, chlorine and fluorine.
2-15C-Alkylen steht für geradkettige oder verzweigte Alkylenreste mit 2 bis 15 Kohlenstoffatomen. Beispielsweise seien die Reste Ethylen (-CH2CH2-), Trimethylen (-CH2CH2CH2-) , Tetramethylen (-CH2CH2CH2CH2-), Pentamethylen (-CH2CH2CH2CH2CH2-), Hexamethylen (-CH2-(CH2)4-CH2-), Octamethylen (-CH2-(CH2)6-CH2-), Decamethylen (-CH2-(CH2)8-CH2-), Tetradecamethylen (-CH2-(CH2)12-CH2-), 1,2-Dimethylethylen [-CH(CH3)-CH(CH3)-], 1,1-Dimethyl- ethylen [-C(CH3)2-CH2-], Isopropyl iden [-C(CH3)2-], 2,2-Dimethylpropylen [-CH2-C(CH3)2-CH2-], 2-Methylpropylen [-CH2-CH(CH3)-CH2-] und 2-Methyl- ethylen [-CH2-CH(CH3)-] genannt.2-15C-Alkylene stands for straight-chain or branched alkylene radicals with 2 to 15 carbon atoms. Examples are ethylene (-CH 2 CH 2 -), trimethylene (-CH 2 CH 2 CH 2 -), tetramethylene (-CH 2 CH 2 CH 2 CH 2 -), pentamethylene (-CH 2 CH 2 CH 2 CH 2 CH 2 -), hexamethylene (-CH 2 - (CH 2 ) 4 -CH 2 -), octamethylene (-CH 2 - (CH 2 ) 6 -CH 2 -), decamethylene (-CH 2 - (CH 2 ) 8 -CH 2 -), tetradecamethylene (-CH 2 - (CH 2 ) 12 -CH 2 -), 1,2-dimethylethylene [-CH (CH 3 ) -CH (CH 3 ) -], 1,1-dimethyl - ethylene [-C (CH 3 ) 2 -CH 2 -], isopropyl idene [-C (CH 3 ) 2 -], 2,2-dimethylpropylene [-CH 2 -C (CH 3 ) 2 -CH 2 -] , 2-methylpropylene [-CH 2 -CH (CH 3 ) -CH 2 -] and 2-methylethylene [-CH 2 -CH (CH 3 ) -] called.
5-7C-Cycloalkylen steht für Cycloalkylenreste mit 5 bis 7 Kohlenstoff¬ atomen. Bevorzugt sind Cyclohexylenreste, wobei beispielsweise der 1,2- und der 1,4-Cyclohexylenrest genannt seien. Di-l-4C-alkylen-5-7C-cycloalkan steht für cyclische Kohlenwasserstoffe mit 5 bis 7 Kohlenstoffatome, die durch zwei (gleiche oder verschiedene) Alky¬ lenreste mit 1 bis 4 Kohlenstoffatomen substituiert sind. Ein bevorzugter Di-l-4C-alkylen-5-7C-cycloalkanrest ist der 1,4-Dimethylencyclohexanrest.5-7C-Cycloalkylene stands for cycloalkylene radicals with 5 to 7 carbon atoms. Cyclohexylene radicals are preferred, the 1,2- and 1,4-cyclohexylene radicals being mentioned, for example. Di-1-4C-alkylene-5-7C-cycloalkane stands for cyclic hydrocarbons with 5 to 7 carbon atoms which are substituted by two (identical or different) alkylene residues with 1 to 4 carbon atoms. A preferred di-1-4C-alkylene-5-7C-cycloalkane radical is the 1,4-dimethylenecyclohexane radical.
Als pharmakologisch verträgliche Salze kommen für Verbindungen der Formel I bevorzugt alle Säureadditionssalze mit in der in der Galenik üblicherwei¬ se verwendeten anorganischen und organischen Säuren in Betracht. Als solche eignen sich wasserlösliche und wasserunlösliche Säureadditionssalze mit Säuren wie beispielsweise Salzsäure, Bromwasserstoffsäure, Phosphorsäure, Salpetersäure, Schwefelsäure, Essigsäure, Zitronensäure, D-Gluconsäure, Benzoesäure, 2-(4-Hydroxybenzoyl)-benzoesäure, Buttersäure, Sulfosalicyl- säure, Maleinsäure, Laurinsäure, Äpfelsäure, Fumarsäure, Bernsteinsäure, Oxalsäure, Weinsäure, Embonsäure, Stearinsäure, Toluolsulfonsäure, Methan- sulfonsäure oder 3-Hydroxy-2-naphtoesäure, wobei die Säuren bei der Salz¬ herstellung - je nachdem, ob es sich um eine ein- oder mehrbasige Säure handelt und je nachdem, welches Salz gewünscht wird - im äqui olaren oder einem davon abweichenden Mengenverhältnis eingesetzt werden.Suitable pharmacologically acceptable salts for compounds of the formula I are preferably all acid addition salts with inorganic and organic acids commonly used in galenics. Suitable as such are water-soluble and water-insoluble acid addition salts with acids such as, for example, hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, acetic acid, citric acid, D-gluconic acid, benzoic acid, 2- (4-hydroxybenzoyl) benzoic acid, butyric acid, sulfosalicylic acid, maleic acid, maleic acid Lauric acid, malic acid, fumaric acid, succinic acid, oxalic acid, tartaric acid, embonic acid, stearic acid, toluenesulfonic acid, methanesulfonic acid or 3-hydroxy-2-naphthoic acid, the acids in the salt production - depending on whether it is a mono- or polybasic acid and, depending on which salt is desired - be used in an equi-olar or a different quantity ratio.
Die Anwendung der Verbindungen der Formel I erfolgt insbesondere in Form solcher Arzneimittel, wie sie für die Behandlung von Augenerkrankungen ge¬ eignet sind. Für die Herstellung der Arzneimittel werden die Verbindungen der Formel I und/oder ihre pharmakologisch verträglichen Salze (= Wirkstof¬ fe) vorzugsweise mit geeigneten pharmazeutischen Hilfsstoffen vermischt und zu geeigneten Arzneiformul ierungen weiterverarbeitet. Als geeignete Arznei¬ formulierungen seien beispielsweise Emulsionen, Suspensionen, Salben oder Lösungen (z.B. Augentropfen) genannt, in denen der Wi kstoffgehalt vorteil¬ hafterweise zwischen 0,01 und 99 % beträgt.The compounds of the formula I are used in particular in the form of those medicaments as are suitable for the treatment of eye diseases. For the preparation of the medicaments, the compounds of the formula I and / or their pharmacologically tolerable salts (= active ingredients) are preferably mixed with suitable pharmaceutical auxiliaries and processed further to form suitable medicament formulations. Suitable pharmaceutical formulations include, for example, emulsions, suspensions, ointments or solutions (e.g. eye drops) in which the amount of hydrogen is advantageously between 0.01 and 99%.
Welche Hilfsstoffe für die gewünschten Arzneiformulierungen geeignet sind, ist dem Fachmann aufgrund seines Fachwissens geläufig. Neben Lösemitteln und anderen Wirkstoffträgem können beispielsweise Antioxidantien, Disper¬ giermittel, Emulgatoren, Konservierungsmittel, Lösungsvermittler oder Per- meationspromotoren verwendet werden. Hervorzuhebende, erfindungsgemäß verwendbare Verbindungen der Formel I sind in den Ansprüchen genannt. Besonders hervorzuheben sind hierbei solche Verbindungen, die systemisch nur eine geringe Wirksamkeit am Herz und/oder Kreislauf zeigen.The person skilled in the art is familiar with the auxiliaries which are suitable for the desired pharmaceutical formulations on the basis of his specialist knowledge. In addition to solvents and other active ingredient carriers, it is possible, for example, to use antioxidants, dispersants, emulsifiers, preservatives, solubilizers or permeation promoters. Compounds of the formula I which can be used according to the invention are mentioned in the claims. Particularly noteworthy here are those compounds that have only a low cardiac and / or circulatory activity systemically.
Die Verbindungen der Formel I sind aus der W092/02503 bekannt. The compounds of formula I are known from WO92 / 02503.
Biologische UntersuchungenBiological studies
Die Verringerung des Augeninnendrucks wurde bei weiblichen Neuseeland-Albi¬ nokaninchen nach üblichen Methoden ermittelt.The reduction in intraocular pressure in female New Zealand albino rabbits was determined using conventional methods.
Die zu untersuchenden Substanzen wurden in 0,05 %iger Lösung (50 μl) in das eine Auge getropft, während in das andere Auge eine Lösung der KontrollSubstanz getropft wurde.The substances to be examined were dropped in 0.05% solution (50 μl) into one eye, while a solution of the control substance was dropped into the other eye.
Durch die Substanz 3,5-Dimethoxycarbonyl-2,6-dimethyl-4-[3-methoxy-2- (2-nitroxyethoxy)phenyl]-l,4-dihydropyridin wird eine Senkung des Augen¬ innendruckes um 19,6 % erzielt. The substance 3,5-dimethoxycarbonyl-2,6-dimethyl-4- [3-methoxy-2- (2-nitroxyethoxy) phenyl] -1,4-dihydropyridine reduces the intraocular pressure by 19.6% .
Claims
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU81427/94A AU8142794A (en) | 1993-11-17 | 1994-11-12 | Use of substituted 1,4-dihydropyridine to reduce intraocular pressure |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH3427/93-2 | 1993-11-17 | ||
| CH342793 | 1993-11-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1995013812A1 true WO1995013812A1 (en) | 1995-05-26 |
Family
ID=4255749
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP1994/003757 Ceased WO1995013812A1 (en) | 1993-11-17 | 1994-11-12 | Use of substituted 1,4-dihydropyridine to reduce intraocular pressure |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU8142794A (en) |
| WO (1) | WO1995013812A1 (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2585574A1 (en) * | 1985-07-31 | 1987-02-06 | Corbiere Jerome | New pharmaceutical compositions for combating glaucoma based on 1,4-dihydropyridines and process for obtaining them |
| EP0289746A2 (en) * | 1987-03-12 | 1988-11-09 | Kyoto Pharmaceutical Industries, Ltd. | 1,4-Dihydropyridine derivatives and pharmaceutical composition thereof |
| WO1992002503A1 (en) * | 1990-08-02 | 1992-02-20 | Cedona Pharmaceuticals Bv | Novel 1,4-dihydropyridine derivatives |
-
1994
- 1994-11-12 WO PCT/EP1994/003757 patent/WO1995013812A1/en not_active Ceased
- 1994-11-12 AU AU81427/94A patent/AU8142794A/en not_active Abandoned
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2585574A1 (en) * | 1985-07-31 | 1987-02-06 | Corbiere Jerome | New pharmaceutical compositions for combating glaucoma based on 1,4-dihydropyridines and process for obtaining them |
| EP0289746A2 (en) * | 1987-03-12 | 1988-11-09 | Kyoto Pharmaceutical Industries, Ltd. | 1,4-Dihydropyridine derivatives and pharmaceutical composition thereof |
| WO1992002503A1 (en) * | 1990-08-02 | 1992-02-20 | Cedona Pharmaceuticals Bv | Novel 1,4-dihydropyridine derivatives |
Non-Patent Citations (1)
| Title |
|---|
| J.A. NATHANSON: "Nitrovasodilators as a new class of ocular hypotensive agents.", J. PHARMACOL. EXP. THER., vol. 260, no. 3, 1992, pages 956 - 965 * |
Also Published As
| Publication number | Publication date |
|---|---|
| AU8142794A (en) | 1995-06-06 |
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