US3737549A - Method of treating depression - Google Patents
Method of treating depression Download PDFInfo
- Publication number
- US3737549A US3737549A US00236180A US3737549DA US3737549A US 3737549 A US3737549 A US 3737549A US 00236180 A US00236180 A US 00236180A US 3737549D A US3737549D A US 3737549DA US 3737549 A US3737549 A US 3737549A
- Authority
- US
- United States
- Prior art keywords
- patients
- trh
- treating depression
- depressant
- observed
- 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.)
- Expired - Lifetime
Links
- 238000000034 method Methods 0.000 title abstract description 9
- 239000000935 antidepressant agent Substances 0.000 abstract description 7
- 230000001430 anti-depressive effect Effects 0.000 abstract description 4
- 239000003795 chemical substances by application Substances 0.000 abstract description 4
- 102000011923 Thyrotropin Human genes 0.000 abstract description 2
- 108010061174 Thyrotropin Proteins 0.000 abstract description 2
- 229960000874 thyrotropin Drugs 0.000 abstract description 2
- 230000001748 thyrotropin Effects 0.000 abstract description 2
- XNSAINXGIQZQOO-SRVKXCTJSA-N protirelin Chemical compound NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H]1NC(=O)CC1)CC1=CN=CN1 XNSAINXGIQZQOO-SRVKXCTJSA-N 0.000 description 13
- 102100032251 Pro-thyrotropin-releasing hormone Human genes 0.000 description 11
- 101800004623 Thyrotropin-releasing hormone Proteins 0.000 description 11
- 229940034199 thyrotropin-releasing hormone Drugs 0.000 description 11
- 230000000694 effects Effects 0.000 description 7
- 230000000994 depressogenic effect Effects 0.000 description 5
- 238000002651 drug therapy Methods 0.000 description 4
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical class OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- BKYUJVHOWQZPQD-UHFFFAOYSA-N 2-[4-[3-(2-chlorophenothiazin-10-yl)propyl]piperazin-1-yl]ethanol;3-(5,6-dihydrodibenzo[2,1-b:2',1'-f][7]annulen-11-ylidene)-n,n-dimethylpropan-1-amine;hydrochloride Chemical compound Cl.C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21.C1CN(CCO)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 BKYUJVHOWQZPQD-UHFFFAOYSA-N 0.000 description 2
- RGCVKNLCSQQDEP-UHFFFAOYSA-N Perphenazine Chemical compound C1CN(CCO)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 RGCVKNLCSQQDEP-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000009945 mood elevation Effects 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- GDLIGKIOYRNHDA-UHFFFAOYSA-N Clomipramine Chemical compound C1CC2=CC=C(Cl)C=C2N(CCCN(C)C)C2=CC=CC=C21 GDLIGKIOYRNHDA-UHFFFAOYSA-N 0.000 description 1
- 206010010144 Completed suicide Diseases 0.000 description 1
- HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 1
- VGOFRWOTSXVPAU-SDDRHHMPSA-N Glu-His-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CCC(=O)O)N)C(=O)O VGOFRWOTSXVPAU-SDDRHHMPSA-N 0.000 description 1
- 206010062767 Hypophysitis Diseases 0.000 description 1
- XNSAINXGIQZQOO-UHFFFAOYSA-N L-pyroglutamyl-L-histidyl-L-proline amide Natural products NC(=O)C1CCCN1C(=O)C(NC(=O)C1NC(=O)CC1)CC1=CN=CN1 XNSAINXGIQZQOO-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- PHVGLTMQBUFIQQ-UHFFFAOYSA-N Nortryptiline Chemical compound C1CC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 PHVGLTMQBUFIQQ-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 206010042458 Suicidal ideation Diseases 0.000 description 1
- 239000000627 Thyrotropin-Releasing Hormone Substances 0.000 description 1
- 229960000836 amitriptyline Drugs 0.000 description 1
- KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 229960004606 clomipramine Drugs 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 229960003914 desipramine Drugs 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229960005426 doxepin Drugs 0.000 description 1
- ODQWQRRAPPTVAG-GZTJUZNOSA-N doxepin Chemical compound C1OC2=CC=CC=C2C(=C/CCN(C)C)/C2=CC=CC=C21 ODQWQRRAPPTVAG-GZTJUZNOSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000002635 electroconvulsive therapy Methods 0.000 description 1
- 229940103472 etrafon Drugs 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 230000002267 hypothalamic effect Effects 0.000 description 1
- 229960004801 imipramine Drugs 0.000 description 1
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 229940060367 inert ingredients Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000000720 neurosecretory effect Effects 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 229960001158 nortriptyline Drugs 0.000 description 1
- 229950004461 noxiptiline Drugs 0.000 description 1
- GPTURHKXTUDRPC-UHFFFAOYSA-N noxiptiline Chemical compound C1CC2=CC=CC=C2C(=NOCCN(C)C)C2=CC=CC=C21 GPTURHKXTUDRPC-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- -1 prothiadin Chemical compound 0.000 description 1
- 229960002601 protriptyline Drugs 0.000 description 1
- BWPIARFWQZKAIA-UHFFFAOYSA-N protriptyline Chemical compound C1=CC2=CC=CC=C2C(CCCNC)C2=CC=CC=C21 BWPIARFWQZKAIA-UHFFFAOYSA-N 0.000 description 1
- WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
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
Definitions
- the present invention relates to an improved method of treating depression.
- anti-depressant agents which are currently used in the treatment of patients sufliering from moderate to severe depression.
- agents include imipramine, desipramine, amitriptyline, nortriptyline, protriptyline, doXepin, prothiadin, Triavil (perphenazine and amitriptyline hydrochloride), Etrafon (perphenazine and amitriptyline hydrochloride), chlorimipramine, noxiptilin and the like. While the above agents have been found to be effective in treating the symptoms of moderate to severe depression, there are several drawbacks to their use.
- the present invention provides such a method.
- TRH thyrotropin releasing hormone
- TRH The anti-depressant activity of TRH was first established in mice using the modified dopa test [Everett, Fed. Proc. 23, p. 198 (1964)].
- the responses in the modified dopa test are graded 1+ for slight increase in activity, 2+ for moderate activity and 3+ for market effects.
- TRH exhibited marked activity at dosages of 0.4 and 0.8 mg./kg. both by the oral and the intraperitoneal routes. Moderate activity was observed at 0.2 mg./kg. i.p. and slight activity at 0.2 mg./kg. p.o. and 0.1 mg./kg. p.o. and i.p.
- TRH a particularly useful anti-depressant agent for the reasons described hereinabove.
- the compound useful in the practice of this invention can be formulated into various pharmaceutical dosage forms such as tablets, capsules, pills, sterile aqueous or non-aqueous solutions for parenteral administration, and the like, for immediate or sustained release, by combining one or more of the active compounds with suitable pharmaceutically acceptable carrier or diluents according to methods well known in the art.
- Such dosage forms may additionally include excipients, binders, fillers, flavoring and sweetening agents and other therapeutically inert ingredients necessary in the formulation of the desired pharmaceutical preparation.
- EXAMPLE 1 Tablets containing 400 mcg. of TRH and having the following composition are prepared according to methods well known in the art.
Landscapes
- 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)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US23618072A | 1972-03-20 | 1972-03-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3737549A true US3737549A (en) | 1973-06-05 |
Family
ID=22888457
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US00236180A Expired - Lifetime US3737549A (en) | 1972-03-20 | 1972-03-20 | Method of treating depression |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US3737549A (OSRAM) |
| AU (1) | AU474598B2 (OSRAM) |
| BE (1) | BE797004A (OSRAM) |
| DE (1) | DE2313635A1 (OSRAM) |
| FR (1) | FR2184595B1 (OSRAM) |
| GB (1) | GB1372664A (OSRAM) |
| PH (1) | PH9926A (OSRAM) |
| ZA (1) | ZA731379B (OSRAM) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3873709A (en) * | 1974-02-19 | 1975-03-25 | Abbott Lab | Method of treating psychosis |
| DE2611976A1 (de) * | 1975-04-03 | 1976-10-14 | Takeda Chemical Industries Ltd | Pharmazeutisches praeparat zur besserung und wiederherstellung bei verminderten bewusstseinszustaenden |
| US5118670A (en) * | 1988-12-14 | 1992-06-02 | Massachusetts Institute Of Technology | Process and composition for increasing brain dopamine release |
| US5830866A (en) * | 1994-09-12 | 1998-11-03 | The Trustees Of The University Of Pennsylvania | Corticotropin release inhibiting factor and methods of using same |
| US6039956A (en) * | 1994-09-12 | 2000-03-21 | Pennsylvania, Trustees Of The University Of, The | Corticotropin release inhibiting factor and methods of using same for treating behavioral symptoms in an anxiety disorder |
| US6475989B1 (en) * | 1997-10-09 | 2002-11-05 | Albert Sattin | Use of pyroglutamyl-glutamyl-prolyl amide (EEP) for neurological and neurobehavioral disorders |
| US20030175350A1 (en) * | 2000-07-11 | 2003-09-18 | Katsuji Sugita | Enteric preparations containing physiologically active peptides |
| US20050009753A1 (en) * | 1997-10-09 | 2005-01-13 | Albert Sattin | Tri-peptides for neurological and neurobehavioral applications |
| US20050233973A1 (en) * | 1997-10-09 | 2005-10-20 | Albert Sattin | Tri-peptides for antidepressant applications |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2227658A (en) * | 1989-02-03 | 1990-08-08 | Cellana | Thyrotropin releasing hormone (trh) composition for enhancing immune function |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3737422A (en) * | 1970-02-04 | 1973-06-05 | Abbott Lab | L-histidyl-l-proline amide |
-
1972
- 1972-03-20 US US00236180A patent/US3737549A/en not_active Expired - Lifetime
-
1973
- 1973-02-27 ZA ZA731379A patent/ZA731379B/xx unknown
- 1973-02-27 GB GB957973A patent/GB1372664A/en not_active Expired
- 1973-03-01 AU AU52799/73A patent/AU474598B2/en not_active Expired
- 1973-03-07 PH PH14394*A patent/PH9926A/en unknown
- 1973-03-19 DE DE2313635A patent/DE2313635A1/de active Pending
- 1973-03-19 BE BE128980A patent/BE797004A/xx not_active IP Right Cessation
- 1973-03-20 FR FR7309994A patent/FR2184595B1/fr not_active Expired
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3873709A (en) * | 1974-02-19 | 1975-03-25 | Abbott Lab | Method of treating psychosis |
| DE2611976A1 (de) * | 1975-04-03 | 1976-10-14 | Takeda Chemical Industries Ltd | Pharmazeutisches praeparat zur besserung und wiederherstellung bei verminderten bewusstseinszustaenden |
| FR2313075A1 (fr) * | 1975-04-03 | 1976-12-31 | Takeda Chemical Industries Ltd | Medicament a base de l-pyroglutamyl-l-histidyl-l-prolinamide ou ses sels |
| US5118670A (en) * | 1988-12-14 | 1992-06-02 | Massachusetts Institute Of Technology | Process and composition for increasing brain dopamine release |
| US5830866A (en) * | 1994-09-12 | 1998-11-03 | The Trustees Of The University Of Pennsylvania | Corticotropin release inhibiting factor and methods of using same |
| US6039956A (en) * | 1994-09-12 | 2000-03-21 | Pennsylvania, Trustees Of The University Of, The | Corticotropin release inhibiting factor and methods of using same for treating behavioral symptoms in an anxiety disorder |
| US6475989B1 (en) * | 1997-10-09 | 2002-11-05 | Albert Sattin | Use of pyroglutamyl-glutamyl-prolyl amide (EEP) for neurological and neurobehavioral disorders |
| US20050009753A1 (en) * | 1997-10-09 | 2005-01-13 | Albert Sattin | Tri-peptides for neurological and neurobehavioral applications |
| US20050233973A1 (en) * | 1997-10-09 | 2005-10-20 | Albert Sattin | Tri-peptides for antidepressant applications |
| US20030175350A1 (en) * | 2000-07-11 | 2003-09-18 | Katsuji Sugita | Enteric preparations containing physiologically active peptides |
Also Published As
| Publication number | Publication date |
|---|---|
| AU474598B2 (en) | 1976-07-29 |
| FR2184595B1 (OSRAM) | 1976-07-02 |
| DE2313635A1 (de) | 1973-10-04 |
| FR2184595A1 (OSRAM) | 1973-12-28 |
| GB1372664A (en) | 1974-11-06 |
| BE797004A (fr) | 1973-09-19 |
| ZA731379B (en) | 1973-11-28 |
| PH9926A (en) | 1976-06-14 |
| AU5279973A (en) | 1974-09-05 |
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