GB2113544A - Treatment of migraine - Google Patents
Treatment of migraine Download PDFInfo
- Publication number
- GB2113544A GB2113544A GB08201892A GB8201892A GB2113544A GB 2113544 A GB2113544 A GB 2113544A GB 08201892 A GB08201892 A GB 08201892A GB 8201892 A GB8201892 A GB 8201892A GB 2113544 A GB2113544 A GB 2113544A
- Authority
- GB
- United Kingdom
- Prior art keywords
- levo
- migraine
- spironolactone
- tryptophan
- mgs
- 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.)
- Withdrawn
Links
- 208000019695 Migraine disease Diseases 0.000 title claims abstract description 18
- 206010027599 migraine Diseases 0.000 title claims abstract description 18
- 229960002256 spironolactone Drugs 0.000 claims abstract description 28
- LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 claims abstract description 28
- 229940000681 5-hydroxytryptophan Drugs 0.000 claims abstract description 13
- 239000000203 mixture Substances 0.000 claims abstract description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- 230000000202 analgesic effect Effects 0.000 claims abstract description 9
- LDCYZAJDBXYCGN-UHFFFAOYSA-N oxitriptan Natural products C1=C(O)C=C2C(CC(N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-UHFFFAOYSA-N 0.000 claims abstract description 3
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 claims description 8
- CPJSUEIXXCENMM-UHFFFAOYSA-N phenacetin Chemical compound CCOC1=CC=C(NC(C)=O)C=C1 CPJSUEIXXCENMM-UHFFFAOYSA-N 0.000 claims description 8
- 230000001154 acute effect Effects 0.000 claims description 6
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 4
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 4
- DEXMFYZAHXMZNM-UHFFFAOYSA-N Narceine Chemical compound OC(=O)C1=C(OC)C(OC)=CC=C1C(=O)CC1=C(CCN(C)C)C=C(OCO2)C2=C1OC DEXMFYZAHXMZNM-UHFFFAOYSA-N 0.000 claims description 4
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 4
- 229960004126 codeine Drugs 0.000 claims description 4
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 claims description 4
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 claims description 4
- XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 claims description 4
- 229960005489 paracetamol Drugs 0.000 claims description 4
- 229960003893 phenacetin Drugs 0.000 claims description 4
- 230000000069 prophylactic effect Effects 0.000 claims description 4
- AKNNEGZIBPJZJG-MSOLQXFVSA-N (-)-noscapine Chemical compound CN1CCC2=CC=3OCOC=3C(OC)=C2[C@@H]1[C@@H]1C2=CC=C(OC)C(OC)=C2C(=O)O1 AKNNEGZIBPJZJG-MSOLQXFVSA-N 0.000 claims description 2
- USSIQXCVUWKGNF-UHFFFAOYSA-N 6-(dimethylamino)-4,4-diphenylheptan-3-one Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 USSIQXCVUWKGNF-UHFFFAOYSA-N 0.000 claims description 2
- 229930008281 A03AD01 - Papaverine Natural products 0.000 claims description 2
- 206010019233 Headaches Diseases 0.000 claims description 2
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 claims description 2
- XADCESSVHJOZHK-UHFFFAOYSA-N Meperidine Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCN(C)CC1 XADCESSVHJOZHK-UHFFFAOYSA-N 0.000 claims description 2
- UQCNKQCJZOAFTQ-ISWURRPUSA-N Oxymorphone Chemical compound O([C@H]1C(CC[C@]23O)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O UQCNKQCJZOAFTQ-ISWURRPUSA-N 0.000 claims description 2
- 229940083712 aldosterone antagonist Drugs 0.000 claims description 2
- 239000002170 aldosterone antagonist Substances 0.000 claims description 2
- AKNNEGZIBPJZJG-UHFFFAOYSA-N alpha-noscapine Natural products CN1CCC2=CC=3OCOC=3C(OC)=C2C1C1C2=CC=C(OC)C(OC)=C2C(=O)O1 AKNNEGZIBPJZJG-UHFFFAOYSA-N 0.000 claims description 2
- UVAZQQHAVMNMHE-XJKSGUPXSA-N alphaprodine Chemical compound C=1C=CC=CC=1[C@@]1(OC(=O)CC)CCN(C)C[C@@H]1C UVAZQQHAVMNMHE-XJKSGUPXSA-N 0.000 claims description 2
- 229960001349 alphaprodine Drugs 0.000 claims description 2
- LKYQLAWMNBFNJT-UHFFFAOYSA-N anileridine Chemical compound C1CC(C(=O)OCC)(C=2C=CC=CC=2)CCN1CCC1=CC=C(N)C=C1 LKYQLAWMNBFNJT-UHFFFAOYSA-N 0.000 claims description 2
- 229960002512 anileridine Drugs 0.000 claims description 2
- 230000002460 anti-migrenic effect Effects 0.000 claims description 2
- 238000002648 combination therapy Methods 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims description 2
- WDEFBBTXULIOBB-WBVHZDCISA-N dextilidine Chemical compound C=1C=CC=CC=1[C@@]1(C(=O)OCC)CCC=C[C@H]1N(C)C WDEFBBTXULIOBB-WBVHZDCISA-N 0.000 claims description 2
- XLMALTXPSGQGBX-GCJKJVERSA-N dextropropoxyphene Chemical compound C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 XLMALTXPSGQGBX-GCJKJVERSA-N 0.000 claims description 2
- 229960004193 dextropropoxyphene Drugs 0.000 claims description 2
- 229960002069 diamorphine Drugs 0.000 claims description 2
- RBOXVHNMENFORY-DNJOTXNNSA-N dihydrocodeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC RBOXVHNMENFORY-DNJOTXNNSA-N 0.000 claims description 2
- 229960000920 dihydrocodeine Drugs 0.000 claims description 2
- XYYVYLMBEZUESM-UHFFFAOYSA-N dihydrocodeine Natural products C1C(N(CCC234)C)C2C=CC(=O)C3OC2=C4C1=CC=C2OC XYYVYLMBEZUESM-UHFFFAOYSA-N 0.000 claims description 2
- -1 dipapanone Chemical compound 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 239000002934 diuretic Substances 0.000 claims description 2
- 230000001882 diuretic effect Effects 0.000 claims description 2
- WGJHHMKQBWSQIY-UHFFFAOYSA-N ethoheptazine Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCCN(C)CC1 WGJHHMKQBWSQIY-UHFFFAOYSA-N 0.000 claims description 2
- 229960000569 ethoheptazine Drugs 0.000 claims description 2
- 229960002428 fentanyl Drugs 0.000 claims description 2
- PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims description 2
- 231100000869 headache Toxicity 0.000 claims description 2
- WVLOADHCBXTIJK-YNHQPCIGSA-N hydromorphone Chemical compound O([C@H]1C(CC[C@H]23)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O WVLOADHCBXTIJK-YNHQPCIGSA-N 0.000 claims description 2
- 229960001410 hydromorphone Drugs 0.000 claims description 2
- 239000006194 liquid suspension Substances 0.000 claims description 2
- 239000002207 metabolite Substances 0.000 claims description 2
- 229960001797 methadone Drugs 0.000 claims description 2
- 238000000034 method Methods 0.000 claims description 2
- NPZXCTIHHUUEEJ-CMKMFDCUSA-N metopon Chemical compound O([C@@]1(C)C(=O)CC[C@@H]23)C4=C5[C@@]13CCN(C)[C@@H]2CC5=CC=C4O NPZXCTIHHUUEEJ-CMKMFDCUSA-N 0.000 claims description 2
- 229950006080 metopon Drugs 0.000 claims description 2
- 229960005181 morphine Drugs 0.000 claims description 2
- PLPRGLOFPNJOTN-UHFFFAOYSA-N narcotine Natural products COc1ccc2C(OC(=O)c2c1OC)C3Cc4c(CN3C)cc5OCOc5c4OC PLPRGLOFPNJOTN-UHFFFAOYSA-N 0.000 claims description 2
- 229960004708 noscapine Drugs 0.000 claims description 2
- 229960005118 oxymorphone Drugs 0.000 claims description 2
- 229960001789 papaverine Drugs 0.000 claims description 2
- VOKSWYLNZZRQPF-GDIGMMSISA-N pentazocine Chemical compound C1C2=CC=C(O)C=C2[C@@]2(C)[C@@H](C)[C@@H]1N(CC=C(C)C)CC2 VOKSWYLNZZRQPF-GDIGMMSISA-N 0.000 claims description 2
- 229960005301 pentazocine Drugs 0.000 claims description 2
- 229960000482 pethidine Drugs 0.000 claims description 2
- ZQHYKVKNPWDQSL-KNXBSLHKSA-N phenazocine Chemical compound C([C@@]1(C)C2=CC(O)=CC=C2C[C@@H]2[C@@H]1C)CN2CCC1=CC=CC=C1 ZQHYKVKNPWDQSL-KNXBSLHKSA-N 0.000 claims description 2
- 229960000897 phenazocine Drugs 0.000 claims description 2
- 208000024891 symptom Diseases 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- 229960001402 tilidine Drugs 0.000 claims description 2
- LDCYZAJDBXYCGN-VIFPVBQESA-N 5-hydroxy-L-tryptophan Chemical compound C1=C(O)C=C2C(C[C@H](N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-VIFPVBQESA-N 0.000 abstract 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
- A61K31/585—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin containing lactone rings, e.g. oxandrolone, bufalin
-
- 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
- A61K31/60—Salicylic acid; Derivatives thereof
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)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Pharmaceutical compositions for treating migraine comprise a mixture of 1-tryptophan or 5-hydroxytryptophan and a spirolactone e.g. spironolactone. A centrally and/or a peripherally acting analgesic can also be present.
Description
SPECIFICATION
Pharmaceutical composition
This invention relates to pharmaceutical compositions for the treatment of migraine.
Migraine, in both its common and classical forms, and its associated disorders, is estimated to affect from 8-12% ofthe population. Numerous compounds have been proposed for the treatment of migraine both on a preventative basis and on an acute basis, but the need still exists for an effective anti-migraine treatment.
In accordance with the present invention, it has been found that combinations of levo-tryptophan, or levo - 5 - hydroxytryptophan, which is a known metabolite of 1-tryptophan, and a spirolactone e.g.
spironolactone is useful in the alleviation of migraine. The use of 1-tryptophan in migraine treatment has been discussed in some detail in 'Headache',
Volume 18, No. 3, (July 1978) page 161, butcom- bination therapy in conjunction with spironolactone is not discussed.
Spironolactone (U.S. Patent 3013 012) is known as an aldosterone antagonist and diuretic and has been reported to have prophylactic properties against migraine, Lancet, May 11th 1968, page 1038.
In another aspect, the present invention provides a method of treating migraine which comprises administering both levo-tryptophan, or levo-5-hydroxytryptophan, and a spirolactone preferably spironolactone.
The pharmaceutical compositions of the present invention are preferably in tablet form for oral administration comprising levo-tryptophan, or levo-5-hydroxytryptophan, and the spirolactone e.g.
spironolactone in admixture in a tabletting carrier. If desired the composition may also include a peripherally acting analgesic, e.g. aspirin, phenacetin or paracetamol, to provide quicker relief of acute symptoms, and/or a centrally acting analgesic such as codeine, morphine, papaverine, noscapine, narceine, dihydrocodeine, dihydromorphinone, oxymorphone, methyldihydromorphinone, heroin, pethidine, alphaprodine, anileridine, ethoheptazine methadone, dipapanone, dextropropoxyphene, phe- nazocine, pentazocine, fentanyl and tilidine.
In the combination therapy of the present invention the effective dose range of levo-tryptophan, or levo-5-hydroxytryptophan is from 5-3000mgs, four to six hourly, preferably 500-1500 mgs, and from 5-400 mgs spironolactone preferably 10-200 mgs.
Tablets for oral administration will be formulated accordingly, conveniently each as a single dosage unit containing from 5-3000 mgs, preferably 5-1500 mgs, levo-tryptophan, or levo-5-hydroxytryptophan, and from 5-400 mgs. Spironolactone preferably 10-200 mgs.
Other formulations, e.g. liquid suspensions, for oral or for rectal administration will be obvious to those skilled in the art.
The compositions of this invention may be given on an acute basis, or as a prophylactic.
1. A pharmaceutical composition for the treatment of migraine comprising in admixture levo-tryptophan, of levo-5-hydroxytryptophan, and a spirolactone.
2. A pharmaceutical composition according to claim 1, wherein said spirolactone is spironolactone.
3. A composition according to claim 1 or 2 additionally containing a centrally or peripherally acting analgesic.
4. A composition according to claim 3, wherein the analgesic is aspirin, phenacetin or paracetamol or codeine.
5. A composition according to any one of the preceding claims in tablet form.
**WARNING** end of DESC field may overlap start of CLMS **.
Claims (5)
1. A pharmaceutical composition for the treatment of migraine comprising in admixture levo-tryptophan, of levo-5-hydroxytryptophan, and a spirolactone.
2. A pharmaceutical composition according to claim 1, wherein said spirolactone is spironolactone.
3. A composition according to claim 1 or 2 additionally containing a centrally or peripherally acting analgesic.
4. A composition according to claim 3, wherein the analgesic is aspirin, phenacetin or paracetamol or codeine.
5. A composition according to any one of the preceding claims in tablet form.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB08201892A GB2113544A (en) | 1982-01-22 | 1982-01-22 | Treatment of migraine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB08201892A GB2113544A (en) | 1982-01-22 | 1982-01-22 | Treatment of migraine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB2113544A true GB2113544A (en) | 1983-08-10 |
Family
ID=10527827
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB08201892A Withdrawn GB2113544A (en) | 1982-01-22 | 1982-01-22 | Treatment of migraine |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB2113544A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996024358A1 (en) * | 1995-02-10 | 1996-08-15 | G.D. Searle & Co. | Use of low dose amount of spironolactone for treatment of cardiovascular disease |
-
1982
- 1982-01-22 GB GB08201892A patent/GB2113544A/en not_active Withdrawn
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996024358A1 (en) * | 1995-02-10 | 1996-08-15 | G.D. Searle & Co. | Use of low dose amount of spironolactone for treatment of cardiovascular disease |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |