US3666859A - 3,4-dicarbethoxy-{62 -phenethylcarbamic acid, ethyl ester in treating depression - Google Patents
3,4-dicarbethoxy-{62 -phenethylcarbamic acid, ethyl ester in treating depression Download PDFInfo
- Publication number
- US3666859A US3666859A US96618A US3666859DA US3666859A US 3666859 A US3666859 A US 3666859A US 96618 A US96618 A US 96618A US 3666859D A US3666859D A US 3666859DA US 3666859 A US3666859 A US 3666859A
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- US
- United States
- Prior art keywords
- ethyl ester
- dicarbethoxy
- phenethylcarbamic acid
- treating depression
- depression
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- 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.)
- Expired - Lifetime
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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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/27—Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
Definitions
- This invention relates to a method for treating the symptoms of depression in mammalian patients using 3,4-dicarbethoxy-B-phenethylcarbamic acid, ethyl ester as the antidepressant agent.
- depression Patients suffering from depression manifest one or more of a variety of symptoms. Generally speaking, depressed patients feel incapable of dealing with their responsibilities. The predominant symptoms of depression are hypochondria, andrexia, insomnia, anergia, anhedonia and pessism. Antidepressant drugs are being widely used to restore patients to a more normal state of mind and thus contribute to the patients physical and mental well-being. However, a number of the drugs produce a variety of undesirable side effects which limit their usefulness, particularly in children and in the elderly.
- the compound can be prepared according to the method described in CA 69 3563 1h (1968). No utilities have previously been reported for the compound. It has now been found that the compound exhibits anti-depressant activity in test animals in dosages of from to 100 mg/kg of body weight daily.
- the anti-depressant activity of the compound useful in the practice of this invention was first established using the modified dopa test described by Everett et al. The Search for New Anti-depressant Drugs, Fed. Proc., 23, p. 198 (1964).
- the modified dopa test is based on the following: when dl- DOPA is given to untreated mice, no response occurs because of the inactivation of the dopa by endogenous monoamine oxidase.
- mice are pre-treated with a monoamine oxidase inhibitor, such as with the oral administration of 40 mg/kg of pargyline hydrochloride (Eutonyl), and are then given 200 mg/kg of dl-DOPA orally, along with a known antidepressant drug, the mice show maximal motor reaction with violent activity, jumping and fighting.
- a monoamine oxidase inhibitor such as with the oral administration of 40 mg/kg of pargyline hydrochloride (Eutonyl)
- dl-DOPA pargyline hydrochloride
- Known anti-depressants such as imipramine and amintryptyline are extremely effective agents in potentiating the dopa response in mice.
- the modified dopa test has been found to be unusually sensitive and reliable in evaluating the anti-depressant activity of potential drugs.
- the response in the dopa test is graded l+for slight increase in activity, 2+ for moderate activity and 3+ for marked effects.
- EXAMPLE 1 The anti-depressant activity of 3,4-dicarbethoxy-B- phenethylcarbamic acid, ethyl ester was evaluated in the above described modified dopa Test 4,8 and 24 hours after oral administration in mice. As can be seen from the following table, the compound exhibited moderate to marked antidepressant effects at dosages of from 5 to 100 mg/kg of body weight. The oral and intraperitoneal LD of the compound in mice is 1000 mg/kg.
- the compound can be administered alone, that is, for example, as the sole ingredient in a filled capsule, it is preferred that the active agent be formulated into a pharmaceutically acceptable dosage form as is customary in the 811.
- Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules.
- the active compound is admixed with at least one inert diluent such as sucrose, lactose or starch.
- Such dosage forms can also comprise, as is normal practice, additional substances other than inert diluents, e.g., lubricating agents such as mag- 3 nesium stearate.
- additional substances other than inert diluents e.g., lubricating agents such as mag- 3 nesium stearate.
- dosage forms may also comprise buffering agents. Tablets and pills can additionally be prepared with enteric coatings.
- Liquid solutions, suspensions, dosage forms for oral administration include, pharmaceutically acceptable emulsions, 35 solutipins, syrups, and elixirs containing inert diluents commonly used in the art, such as water. Besides inert diluents, such compositions can also include adjuvants, such as wetting agents, emulsifying and suspending agents, and sweetening, flavoring and perfuming agents.
- Preparations according to this invention for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions or emulsions.
- non-aqueous solvents or vehicles are propylene glycol, polyethylene glycol, vegetable oils, such as olive oil and injectable organic esters such as ethyl oleate.
- Such dosage forms may also contain adjuvants such as preserving, wetting, emulsifying and dispersing agents. They may be sterilized by, for example, filtration through a bacteria-retaining filter, by incorporating sterilizing agents into the compositions, by irradiating the compositions, or by heating the compositions. They can also be manufactured in the form of sterile solid compositions which can be dissolved in sterile water, or some other sterile injectable medium immediately before use.
- compositions for rectal administration are suppositories which may contain in addition to the active substance, excipients such as cocoa butter or a suppository wax.
- the dosage of active ingredient in the compositions of this invention may be varied; however, it is necessary that the amount of the active ingredient shall be such that a suitable dosage form is obtained.
- the selected dosage depends upon the desired therapeutic effect, on the route of administration, and on the duration of the treatment.
- I claim 1 A method of treating a patient exhibiting the symptoms of depression comprising administering a therapeutically effective amount of 3,4-dicarbethoxy-B-phenethylcarbamic acid, ethyl ester, to a depressed patient.
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- Health & Medical Sciences (AREA)
- Emergency Medicine (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)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
A method of treating the symptoms of depression comprising administering a therapeutically effective amount of 3,4dicarbethoxy- Beta -phenethylcarbamic acid, ethyl ester to patients in need of such treatment.
Description
United States Patent Plotnikoff 51 May 30, 1972 [54] 3,4-DICARBETHOXY-B- PHENETHYLCARBANIIC ACID, ETHYL ESTER IN TREATING DEPRESSION [72] Inventor: Nicholas Peter Plotnikofi, Lake Bluff, Ill.
[73] Assignee: Abbott Laboratories, North Chicago, Ill.
[22] Filed: Dec. 9, 1970 [21] App]. No.: 96,618
52 U.S. c1 ..424/300 51 lnt.Cl. [58] FieldoiSearch ..424/300 [5 6] References Cited OTHER PUBLICATIONS Chem. Abst. 69 35631 h (1968).
Primary Examiner-Stanley J. Friedman AttorneyRobert L. Niblack [57] ABSTRACT 2 Claims, No Drawings 3 ,4-DICARBETHOXY-B-PHENETHYLCARBAMIC ACID, ETHYL ESTER IN TREATING DEPRESSION This invention relates to a method for treating the symptoms of depression in mammalian patients using 3,4-dicarbethoxy-B-phenethylcarbamic acid, ethyl ester as the antidepressant agent.
Patients suffering from depression manifest one or more of a variety of symptoms. Generally speaking, depressed patients feel incapable of dealing with their responsibilities. The predominant symptoms of depression are hypochondria, andrexia, insomnia, anergia, anhedonia and pessism. Antidepressant drugs are being widely used to restore patients to a more normal state of mind and thus contribute to the patients physical and mental well-being. However, a number of the drugs produce a variety of undesirable side effects which limit their usefulness, particularly in children and in the elderly.
Accordingly, it is an object of this invention to provide a method for relieving the symptoms of depression in patients in need of such treatment without producing adverse side effects.
The compound useful in the practice of this invention, 3,4- dicarbethoxy-B-phenethylcarbamic acid, ethyl ester, is represented by the structural formula:
The compound can be prepared according to the method described in CA 69 3563 1h (1968). No utilities have previously been reported for the compound. It has now been found that the compound exhibits anti-depressant activity in test animals in dosages of from to 100 mg/kg of body weight daily.
The anti-depressant activity of the compound useful in the practice of this invention was first established using the modified dopa test described by Everett et al. The Search for New Anti-depressant Drugs, Fed. Proc., 23, p. 198 (1964). The modified dopa test is based on the following: when dl- DOPA is given to untreated mice, no response occurs because of the inactivation of the dopa by endogenous monoamine oxidase. However, if mice are pre-treated with a monoamine oxidase inhibitor, such as with the oral administration of 40 mg/kg of pargyline hydrochloride (Eutonyl), and are then given 200 mg/kg of dl-DOPA orally, along with a known antidepressant drug, the mice show maximal motor reaction with violent activity, jumping and fighting. Known anti-depressants such as imipramine and amintryptyline are extremely effective agents in potentiating the dopa response in mice. Thus, the modified dopa test has been found to be unusually sensitive and reliable in evaluating the anti-depressant activity of potential drugs. The response in the dopa test is graded l+for slight increase in activity, 2+ for moderate activity and 3+ for marked effects.
The following example illustrates this invention.
EXAMPLE 1 The anti-depressant activity of 3,4-dicarbethoxy-B- phenethylcarbamic acid, ethyl ester was evaluated in the above described modified dopa Test 4,8 and 24 hours after oral administration in mice. As can be seen from the following table, the compound exhibited moderate to marked antidepressant effects at dosages of from 5 to 100 mg/kg of body weight. The oral and intraperitoneal LD of the compound in mice is 1000 mg/kg.
TABLE I Anti-Depressant Activity of 3,4-Dicarbethoxy-[3-Phenethyl- Carbamic Acid, Ethyl Ester 4,8 and 24 Hours After Oral In the practice of this invention, patients suffering from depression receive from 5 to 100 mg/kg of body weight daily of 3,4-dicarbethoxy-B-phenethylcarbamic acid, ethyl ester, either in single or divided doses. While the compound exhibits activity by both oral and parenteral routes, oral administration is preferred.
While the compound can be administered alone, that is, for example, as the sole ingredient in a filled capsule, it is preferred that the active agent be formulated into a pharmaceutically acceptable dosage form as is customary in the 811.
Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In such solid dosage forms, the active compound is admixed with at least one inert diluent such as sucrose, lactose or starch. Such dosage forms can also comprise, as is normal practice, additional substances other than inert diluents, e.g., lubricating agents such as mag- 3 nesium stearate. In the case of capsules, tablets and pills, the
dosage forms may also comprise buffering agents. Tablets and pills can additionally be prepared with enteric coatings.
Liquid solutions, suspensions, dosage forms for oral administration include, pharmaceutically acceptable emulsions, 35 solutipins, syrups, and elixirs containing inert diluents commonly used in the art, such as water. Besides inert diluents, such compositions can also include adjuvants, such as wetting agents, emulsifying and suspending agents, and sweetening, flavoring and perfuming agents.
Preparations according to this invention for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions or emulsions. Examples of non-aqueous solvents or vehicles are propylene glycol, polyethylene glycol, vegetable oils, such as olive oil and injectable organic esters such as ethyl oleate. Such dosage forms may also contain adjuvants such as preserving, wetting, emulsifying and dispersing agents. They may be sterilized by, for example, filtration through a bacteria-retaining filter, by incorporating sterilizing agents into the compositions, by irradiating the compositions, or by heating the compositions. They can also be manufactured in the form of sterile solid compositions which can be dissolved in sterile water, or some other sterile injectable medium immediately before use.
Compositions for rectal administration are suppositories which may contain in addition to the active substance, excipients such as cocoa butter or a suppository wax.
The dosage of active ingredient in the compositions of this invention may be varied; however, it is necessary that the amount of the active ingredient shall be such that a suitable dosage form is obtained. The selected dosage depends upon the desired therapeutic effect, on the route of administration, and on the duration of the treatment.
I claim 1. A method of treating a patient exhibiting the symptoms of depression comprising administering a therapeutically effective amount of 3,4-dicarbethoxy-B-phenethylcarbamic acid, ethyl ester, to a depressed patient.
2. A method in accordance with claim 1 wherein the compound is administered to a depressed patient in dosages of 70 from 1 to 100 mg./kg. of body weight daily.
Claims (1)
- 2. A method in accordance with claim 1 wherein the compound is administered to a depressed patient in dosages of from 1 to 100 mg./kg. of body weight daily.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US9661870A | 1970-12-09 | 1970-12-09 |
Publications (1)
Publication Number | Publication Date |
---|---|
US3666859A true US3666859A (en) | 1972-05-30 |
Family
ID=22258248
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US96618A Expired - Lifetime US3666859A (en) | 1970-12-09 | 1970-12-09 | 3,4-dicarbethoxy-{62 -phenethylcarbamic acid, ethyl ester in treating depression |
Country Status (4)
Country | Link |
---|---|
US (1) | US3666859A (en) |
DE (1) | DE2160898A1 (en) |
FR (1) | FR2117957B1 (en) |
ZA (1) | ZA717658B (en) |
-
1970
- 1970-12-09 US US96618A patent/US3666859A/en not_active Expired - Lifetime
-
1971
- 1971-11-15 ZA ZA717658A patent/ZA717658B/en unknown
- 1971-12-08 FR FR7144103A patent/FR2117957B1/fr not_active Expired
- 1971-12-08 DE DE19712160898 patent/DE2160898A1/en active Pending
Non-Patent Citations (1)
Title |
---|
Chem. Abst. 69 35631 h (1968). * |
Also Published As
Publication number | Publication date |
---|---|
ZA717658B (en) | 1972-08-30 |
DE2160898A1 (en) | 1972-06-22 |
FR2117957B1 (en) | 1974-10-18 |
FR2117957A1 (en) | 1972-07-28 |
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