CA2127573A1 - Vasotonic treatment for migraines - Google Patents
Vasotonic treatment for migrainesInfo
- Publication number
- CA2127573A1 CA2127573A1 CA 2127573 CA2127573A CA2127573A1 CA 2127573 A1 CA2127573 A1 CA 2127573A1 CA 2127573 CA2127573 CA 2127573 CA 2127573 A CA2127573 A CA 2127573A CA 2127573 A1 CA2127573 A1 CA 2127573A1
- Authority
- CA
- Canada
- Prior art keywords
- agents
- migraine
- migraines
- headaches
- tryptophan
- 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.)
- Abandoned
Links
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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
-
- 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
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
- A61K33/10—Carbonates; Bicarbonates
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)
- Inorganic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
A novel composition of five extant agents was hypothesized, tested, and confirmed for alleviating migraine headaches. The hypothesis was based on ways to correct three features of migraines--falling blood levels of serotonin, vasodilatation, and inflammatory response--using already existing agents. The composition successfully aborted migraines within 30 to 60 minutes, sometimes requiring a repeat four hours later if symptoms returned. Two of the five components--acetylsalicylic acid and caffeine--are already used for treating headaches, yet it was the combination of these two and three other agents--niacin, calcium, and L-tryptophan--that successfully alleviated migraines. Once taken, subjects are not to consume high-potassium food or drinkfor several hours as potassium causes vasodilatation, militating against effortsto enhance vasoconstriction. Other migraine medications risk rebound headaches,serious side effects like cardiac ischemia or paresthesia in the extremities, and drug addiction (some contain a barbiturate and/or narcotic). The five components risk only minor side effects and are used at low-to-very-low doses, further reducing the risk of adverse effects. Apart from occasional flushing from niacin, no side effects or rebound headaches have been reported in migraineurs using this from 1 - 2 1/2 years. No one has previously reported combining these five agents intentionally or serendipitously. No one has reported using tryptophan or calcium for headaches, so the combination of all five agents was not obvious. This migraine treatment resulted from scientific hypothesis-testing, not from serendipity or an "obvious" combining of agents.
Description
Niacin-Calcium-Caffeine-Acetylsalicylic-Acid With Tryptophan Treatment For Migraines The present invention of a novel composition relates to a treatment for alleviating migraine headaches. Although two of the five components, namely, acetylsalicylic acid and caffeine, are already used for treating headaches, it is the addition of the other agents that relates to the novel composition for use in alleviating mi~raine headaches.
Several medicinal treatments for migraines are known, although none claims effectiveness with all migraine patients. One medication called 10 sumatriptan, a serotonin type lD receptor agonist, has been reported effective in aborting migraines in 70% to 80% of migraineurs (Ferrari &
Saxena, 1993; Pearce, 1992). Sumatriptan has been reported to cause rebound migraine headaches within 48 hours after use in one-third to 42% of patients (Ferrari & Saxena, 1993; Pearce, 1992). Sumatriptan has been reported to cause adverse effects on the heart by constricting coronary arteries and occasionally causing cardiac ischemia in some patients, a serious side effect (Ferrari & Saxena, 1993). The current high cost was reported as one of the limits to sumatriptan's use (Pearce, 1992).
Other migraine medication can cause paresthesia, pain and weakness in the 20 extremities, specifically ergotamine with caffeine, tradename "Cafergot"
(Compendium of Pharmaceuticals and Specialties, 1993). Others contain addictive substances such as a barbiturate or a narcotic, and may cause physical dependency. For example, the migraine medication tradename "Fiorinal" contains acetylsalicylic acid, caffeine, and the barbiturate butalbital; "Fiorinal-C" contains acetylsalicylic acid, caffeine, butalbital, and the narcotic codeine. The medication tr~d~n; e "Tylenol #3" contains caffeine, acetaminophen, the narcotic codeine, and is used for headache pain (Compendium of Pharmaceuticals and Specialties, 1993).
-Physiologic events occurring during migraine attacks include but are not limited to the following: falling blood levels of serotonin (Anthony & Lance, 1971; Anthony & Lance 1989); vascular dilatation (Dalessio, 1979; Ferrari and associates, 1991); inflammatory response in intracranial structures (Pearce, 1992); and in some not all migraines, an increasing release of histamine still rising 24 hours after onset (Anthony & Lance, 1971).
Migraine medications containing substances that affect blood vessel tone, such as vasoconstriction, could be expected to alleviate the migraine feature of vasodilatation and/or irregularities of vasodilatation and 10 vasoconstriction. Migraine medications cont~ining substances that enhance serotonergic functioning might be expected to alleviate the migraine feature of falling blood levels of serotonin and/or the vascular sequelae caused by diminished serotonin blood levels. Most migraine medications individually influence only one or two of the first three physiologic events mentioned.
One medication that does influence these three physiologic features is sumatriptan (Ferrari & Saxena, 1993), but it can cause rebound headaches and other side effects.
The inventor hypothesized that extant agents ~nown to influence these three physiologic features of migraines might be useful in treating 20 migraines. The inventor, a researcher who had already published several studies involving serotonin, theorized that:
to reverse a decreasing blood level of serotonin, L-trYPtoPhan, a precursor of serotonin, can be used;
to restore serotonin's influence in regulating blood vessel tone, reversing the decreasing blood level of serotonin is required, and acetYlsalicYlic acid can displace tryptophan from binding proteins, thereby freeing up more tryptophan for serotonin synthesis (Chafetz, 1990, p. 61).
f~, to facilitate tryptophan's conversion to serotonin instead of conversion to kynurenines and/or nicotinic acid, niacin, which is also called nicotinic acid, is effective because it is a feedback regulator for the kynurenine pathway of tryptophan metabolism, and it reduces the amount of tryptophan converted to kynurenines (Lapin, 1991).
to reduce vasodilatation, agents with vasoconstricting properties such as caffeine (Leonard et al., 1987) or calcium (Guyton, 1986, p. 243) are useful;
to reduce vasodilatation, avoiding food and drink high in potassium, a mineral that causes vasodilatation (Guyton, 1986, p. 243), is a logical proscription;
to reduce an inflammatory response, ascetYlsalicYlic acid can be used.
Except for the amino acid L-tryptophan, which requires a medical prescription, the other agents require no prescription, are commonly available and, at low doses, no serious risks are reported (Compendium of Pharmaceuticals and Specialties, 1993; Hendler, 1990).
The first time this hypothesized combination of five agents was tested, it terminated the migraine with no side effects or rebound headache. The inventor was the first subject, thereby ensuring no one was put at undue 20 risk. Two and a half years of data have been collected on the first subject.
That evidence and subsequent data on others indicate that the hypothesized composition alleviates migraines within 30 to 60 minutes and does not cause recurring headaches 24 or 48 hours later. Apart from occasional flushing of the face and/or upper body lasting 15 to 30 minutes, no side effects have been reported in the small number of migraineurs who have tried this treatment to date. These subjects had had migraines for at least 8 years, have a family history of migraines, and previously had debilitating migraines necessitating retreat to bed. Further studies are in progress.
21275~3 This novel composition overcomes disadvantages posed by previous treatments because, at worst, only minor side effects are listed in the standard medication reference (Compendium of Pharmaceuticals and Specialties, 1993) for low doses of these common agents, and low-to-very-low doses are used. This is consistent with the evidence so far. Apart from occasional flushing, a "harmless" response to niacin (Stern et al., 1991, p. 66), no side effects have been reported by migraineurs who tried this over a period of 1 - 2 1/2 years. No rebound headaches 24 hours later have occurred during that time period either. The caffeine component entails only low doses. The 10 other four agents are not known to have addictive properties.
Another advantage is that the cost of these common agents is rather modest, and only a small fraction of the cost of the currently most effective migraine treatment, sumatriptan. This could mean that migraine sufferers on low incomes could more easily avail themselves of this approach. The novel composition is used only when needed. This contrasts with preventative migraine medications which are ta~en daily, thereby incurring the cost of daily medication plus concomitant ris~ of side effects with long-term use.
This novel treatment has been repeatedly effective at the doses listed.
The invention consists of the following agents and directions for use:
100 milligrams vitamin B3 niacin;
500 lligrams calcium carbonate;
64 milligrams caffeine;
650 lligrams acetylsalicylic acid;
500 ll;grams amino acid L-tryptophan, which requires a prescription;
ta~en orally with 120 ll;litres of milk when one realizes one has a migraine or awa~es with a migraine; all can be repeated four hours later if migraine symptoms return, up to two repeats;
once ta~en, high-potassium foods are to be avoided for several hours.
-The standard practice of avoiding consumption of hot liquids in the hour after taking niacin, applies because of the possibility of flushing (Stern et al., 1991). The standard practice of ta~ing food or drin~ with niacin or tryptophan is met with the small consumption of milk. However, the composition works when ta~en with water if one is in a situation without mil~
immediately available.
Doses of 1 gram L-tryptophan have also been found effective, but this is the suggested upper range Per intake because single doses higher than 1 gram approach a "loading dose" of tryptophan. Loading doses activate the enzyme, 10 tryptophan pyrrolase, that routes tryptophan down the ~ynurenine pathway away from conversion to serotonin (Gal & Sherman, 1980). Doses of caffeine could range up to 100 lligrams per inta~e and still obtain benefit.
A subcombination of the novel combination, consisting of all the agents minus the L-tryptophan, has been found to provide some benefit. Preliminary evidence suggests that this subcombination halts a migraine from worsening but symptoms present before intake may linger a few hours before disappearing. This contrasts with recovery 30 to 60 minutes after inta~e that has been found when all five agents are used.
Some migraine episodes have a concomitant strong release of histamine 20 that continues to increase 24 hours after onset (Anthony & Lance, 1971).
Not all migraineurs have seasonal allergies, but migraineurs who do have a sensitivity to pollens might have this escalating-histamine variation when exposed to certain plant substances. Migraineurs sensitive to rapid barometric pressure changes, might have the escalating-histamine migraine version when travelling by airplane or during fast weather changes. If benefit were not obtained with the novel composition, the addition of a histamine type 1 receptor bloc~er, such as a non-sedating 12-hour antihistamine terfenadine, has been effective.
All five agents have been in use with humans for decades or longer, yet there are no reports of these five being combined therapeutically. Niacin alone for migraines has been mentioned anecdotally (Hendler, 1990, p. 60).
Caffeine and/or acetylsalicylic acid are common co-agents in migraine medication. But no other migraine medication includes tryptophan or calcium.
For these reasons, the inventor regards this novel composition as an unobvious choice of agents to combine. All but L-tryptophan are readily available in tablet form--at these doses--not requiring a prescription;
L-tryptophan requires a prescription in Canada.
No one has previously reported combining these five common agents intentionally or serendipitously for a treatment effect. Numerous scientists have striven to create effective migraine treatment, and current research focuses on designing new drugs, not on using extant agents in new combinations. The idea to combine these five agents was done by the inventor first hypothesizing what might correct three physiologic features of migraines, then by testing the hypothesis on a migraine subject who happened to be the inventor. The first time this hypothesized combination was tried, it terminated the first of many migraines with no side effects or rebound headache; this occurred February 27, 1992. This novel treatment is the 20 outcome of scientific hypothesis-testing, not of serendipity or an "obvious"
combining of agents.
References to publications cited herein follow.
Anthony, M. & Lance, J.W. (1971) Histamine and serotonin in cluster headache.
Archives of Neurolo~Y 25, 225-231.
Anthony, M. & Lance, J.W. (1989) Plasma serotonin in patients with chronic headaches. Journal of Neurolo~Y, Neurosur~erY. and PsYchiatrY 52, 182-184.
Chafetz, M.D. (1990) Nutrition and Neurotransmitters~ The Nutrient Bases of Behavior. Prentice Hall: Englewood Cliffs, New Jersey.
-Canadian Pharmaceutical Association. (1993) ComPendium of Pharmaceuticals and SPecialties. TwentY-Ei~hth Edition. Canadian Pharmaceutical Association:
Ottawa, Canada.
Dalessio, D. (1979) Classification and mechanism of migraine. Headache 19, 114-119.
Ferrari, M.D. & Subcutaneous Sumatriptan International Study Group. (1991) Treatment of migraine attacks with sumatriptan. New En~land Journal of Medicine 325, 316-321.
Ferrari, M.D. & Saxena, P.R. (1993) Clinical and experimental effects of sumatriptan in humans. Trends in Pharmacolo~ical Sciences 14, 129-133.
Gal, E. & Sherman, A.D. (1980) L-kynurenine, its synthesis and possible regulatory function in brain. Neurochemical Research 5, 223-229.
Guyton, A.C. (1986) Textbook of Medical PhYsiolo~Y. Seventh Edition.
W.B. Saunders: Toronto, Canada.
Hendler, S.S. (1990) The Doctors' Vitamin and Mineral EncYcloPedia. Simon &
Schuster: New York, N.Y.
Lapin, I.P. (1991) Kynurenines and seizures. EPilePsia 22, 257-265.
Leonard, T.K., Watson, R.R. & Mohs, M.E. (1987) The effects of caffeine on various body systems: a review. Journal of the American Dietetic Association 87, 1048-1053.
Pearce, J.M.S. (1992) Sumatriptan: efficacy and contribution to migraine me~h~n; ~. Journal of Neurolo~Y. Neurosur~erY. and PsYchiatrY 55, 1103-1105.
Stern, R.H., Spence, D., Freeman, D.J., Parbtani, A. (1991) Tolerance to nicotinic acid flushing. Clinical Pharmacolo~Y and TheraPeutics 50, 66-70.
Several medicinal treatments for migraines are known, although none claims effectiveness with all migraine patients. One medication called 10 sumatriptan, a serotonin type lD receptor agonist, has been reported effective in aborting migraines in 70% to 80% of migraineurs (Ferrari &
Saxena, 1993; Pearce, 1992). Sumatriptan has been reported to cause rebound migraine headaches within 48 hours after use in one-third to 42% of patients (Ferrari & Saxena, 1993; Pearce, 1992). Sumatriptan has been reported to cause adverse effects on the heart by constricting coronary arteries and occasionally causing cardiac ischemia in some patients, a serious side effect (Ferrari & Saxena, 1993). The current high cost was reported as one of the limits to sumatriptan's use (Pearce, 1992).
Other migraine medication can cause paresthesia, pain and weakness in the 20 extremities, specifically ergotamine with caffeine, tradename "Cafergot"
(Compendium of Pharmaceuticals and Specialties, 1993). Others contain addictive substances such as a barbiturate or a narcotic, and may cause physical dependency. For example, the migraine medication tradename "Fiorinal" contains acetylsalicylic acid, caffeine, and the barbiturate butalbital; "Fiorinal-C" contains acetylsalicylic acid, caffeine, butalbital, and the narcotic codeine. The medication tr~d~n; e "Tylenol #3" contains caffeine, acetaminophen, the narcotic codeine, and is used for headache pain (Compendium of Pharmaceuticals and Specialties, 1993).
-Physiologic events occurring during migraine attacks include but are not limited to the following: falling blood levels of serotonin (Anthony & Lance, 1971; Anthony & Lance 1989); vascular dilatation (Dalessio, 1979; Ferrari and associates, 1991); inflammatory response in intracranial structures (Pearce, 1992); and in some not all migraines, an increasing release of histamine still rising 24 hours after onset (Anthony & Lance, 1971).
Migraine medications containing substances that affect blood vessel tone, such as vasoconstriction, could be expected to alleviate the migraine feature of vasodilatation and/or irregularities of vasodilatation and 10 vasoconstriction. Migraine medications cont~ining substances that enhance serotonergic functioning might be expected to alleviate the migraine feature of falling blood levels of serotonin and/or the vascular sequelae caused by diminished serotonin blood levels. Most migraine medications individually influence only one or two of the first three physiologic events mentioned.
One medication that does influence these three physiologic features is sumatriptan (Ferrari & Saxena, 1993), but it can cause rebound headaches and other side effects.
The inventor hypothesized that extant agents ~nown to influence these three physiologic features of migraines might be useful in treating 20 migraines. The inventor, a researcher who had already published several studies involving serotonin, theorized that:
to reverse a decreasing blood level of serotonin, L-trYPtoPhan, a precursor of serotonin, can be used;
to restore serotonin's influence in regulating blood vessel tone, reversing the decreasing blood level of serotonin is required, and acetYlsalicYlic acid can displace tryptophan from binding proteins, thereby freeing up more tryptophan for serotonin synthesis (Chafetz, 1990, p. 61).
f~, to facilitate tryptophan's conversion to serotonin instead of conversion to kynurenines and/or nicotinic acid, niacin, which is also called nicotinic acid, is effective because it is a feedback regulator for the kynurenine pathway of tryptophan metabolism, and it reduces the amount of tryptophan converted to kynurenines (Lapin, 1991).
to reduce vasodilatation, agents with vasoconstricting properties such as caffeine (Leonard et al., 1987) or calcium (Guyton, 1986, p. 243) are useful;
to reduce vasodilatation, avoiding food and drink high in potassium, a mineral that causes vasodilatation (Guyton, 1986, p. 243), is a logical proscription;
to reduce an inflammatory response, ascetYlsalicYlic acid can be used.
Except for the amino acid L-tryptophan, which requires a medical prescription, the other agents require no prescription, are commonly available and, at low doses, no serious risks are reported (Compendium of Pharmaceuticals and Specialties, 1993; Hendler, 1990).
The first time this hypothesized combination of five agents was tested, it terminated the migraine with no side effects or rebound headache. The inventor was the first subject, thereby ensuring no one was put at undue 20 risk. Two and a half years of data have been collected on the first subject.
That evidence and subsequent data on others indicate that the hypothesized composition alleviates migraines within 30 to 60 minutes and does not cause recurring headaches 24 or 48 hours later. Apart from occasional flushing of the face and/or upper body lasting 15 to 30 minutes, no side effects have been reported in the small number of migraineurs who have tried this treatment to date. These subjects had had migraines for at least 8 years, have a family history of migraines, and previously had debilitating migraines necessitating retreat to bed. Further studies are in progress.
21275~3 This novel composition overcomes disadvantages posed by previous treatments because, at worst, only minor side effects are listed in the standard medication reference (Compendium of Pharmaceuticals and Specialties, 1993) for low doses of these common agents, and low-to-very-low doses are used. This is consistent with the evidence so far. Apart from occasional flushing, a "harmless" response to niacin (Stern et al., 1991, p. 66), no side effects have been reported by migraineurs who tried this over a period of 1 - 2 1/2 years. No rebound headaches 24 hours later have occurred during that time period either. The caffeine component entails only low doses. The 10 other four agents are not known to have addictive properties.
Another advantage is that the cost of these common agents is rather modest, and only a small fraction of the cost of the currently most effective migraine treatment, sumatriptan. This could mean that migraine sufferers on low incomes could more easily avail themselves of this approach. The novel composition is used only when needed. This contrasts with preventative migraine medications which are ta~en daily, thereby incurring the cost of daily medication plus concomitant ris~ of side effects with long-term use.
This novel treatment has been repeatedly effective at the doses listed.
The invention consists of the following agents and directions for use:
100 milligrams vitamin B3 niacin;
500 lligrams calcium carbonate;
64 milligrams caffeine;
650 lligrams acetylsalicylic acid;
500 ll;grams amino acid L-tryptophan, which requires a prescription;
ta~en orally with 120 ll;litres of milk when one realizes one has a migraine or awa~es with a migraine; all can be repeated four hours later if migraine symptoms return, up to two repeats;
once ta~en, high-potassium foods are to be avoided for several hours.
-The standard practice of avoiding consumption of hot liquids in the hour after taking niacin, applies because of the possibility of flushing (Stern et al., 1991). The standard practice of ta~ing food or drin~ with niacin or tryptophan is met with the small consumption of milk. However, the composition works when ta~en with water if one is in a situation without mil~
immediately available.
Doses of 1 gram L-tryptophan have also been found effective, but this is the suggested upper range Per intake because single doses higher than 1 gram approach a "loading dose" of tryptophan. Loading doses activate the enzyme, 10 tryptophan pyrrolase, that routes tryptophan down the ~ynurenine pathway away from conversion to serotonin (Gal & Sherman, 1980). Doses of caffeine could range up to 100 lligrams per inta~e and still obtain benefit.
A subcombination of the novel combination, consisting of all the agents minus the L-tryptophan, has been found to provide some benefit. Preliminary evidence suggests that this subcombination halts a migraine from worsening but symptoms present before intake may linger a few hours before disappearing. This contrasts with recovery 30 to 60 minutes after inta~e that has been found when all five agents are used.
Some migraine episodes have a concomitant strong release of histamine 20 that continues to increase 24 hours after onset (Anthony & Lance, 1971).
Not all migraineurs have seasonal allergies, but migraineurs who do have a sensitivity to pollens might have this escalating-histamine variation when exposed to certain plant substances. Migraineurs sensitive to rapid barometric pressure changes, might have the escalating-histamine migraine version when travelling by airplane or during fast weather changes. If benefit were not obtained with the novel composition, the addition of a histamine type 1 receptor bloc~er, such as a non-sedating 12-hour antihistamine terfenadine, has been effective.
All five agents have been in use with humans for decades or longer, yet there are no reports of these five being combined therapeutically. Niacin alone for migraines has been mentioned anecdotally (Hendler, 1990, p. 60).
Caffeine and/or acetylsalicylic acid are common co-agents in migraine medication. But no other migraine medication includes tryptophan or calcium.
For these reasons, the inventor regards this novel composition as an unobvious choice of agents to combine. All but L-tryptophan are readily available in tablet form--at these doses--not requiring a prescription;
L-tryptophan requires a prescription in Canada.
No one has previously reported combining these five common agents intentionally or serendipitously for a treatment effect. Numerous scientists have striven to create effective migraine treatment, and current research focuses on designing new drugs, not on using extant agents in new combinations. The idea to combine these five agents was done by the inventor first hypothesizing what might correct three physiologic features of migraines, then by testing the hypothesis on a migraine subject who happened to be the inventor. The first time this hypothesized combination was tried, it terminated the first of many migraines with no side effects or rebound headache; this occurred February 27, 1992. This novel treatment is the 20 outcome of scientific hypothesis-testing, not of serendipity or an "obvious"
combining of agents.
References to publications cited herein follow.
Anthony, M. & Lance, J.W. (1971) Histamine and serotonin in cluster headache.
Archives of Neurolo~Y 25, 225-231.
Anthony, M. & Lance, J.W. (1989) Plasma serotonin in patients with chronic headaches. Journal of Neurolo~Y, Neurosur~erY. and PsYchiatrY 52, 182-184.
Chafetz, M.D. (1990) Nutrition and Neurotransmitters~ The Nutrient Bases of Behavior. Prentice Hall: Englewood Cliffs, New Jersey.
-Canadian Pharmaceutical Association. (1993) ComPendium of Pharmaceuticals and SPecialties. TwentY-Ei~hth Edition. Canadian Pharmaceutical Association:
Ottawa, Canada.
Dalessio, D. (1979) Classification and mechanism of migraine. Headache 19, 114-119.
Ferrari, M.D. & Subcutaneous Sumatriptan International Study Group. (1991) Treatment of migraine attacks with sumatriptan. New En~land Journal of Medicine 325, 316-321.
Ferrari, M.D. & Saxena, P.R. (1993) Clinical and experimental effects of sumatriptan in humans. Trends in Pharmacolo~ical Sciences 14, 129-133.
Gal, E. & Sherman, A.D. (1980) L-kynurenine, its synthesis and possible regulatory function in brain. Neurochemical Research 5, 223-229.
Guyton, A.C. (1986) Textbook of Medical PhYsiolo~Y. Seventh Edition.
W.B. Saunders: Toronto, Canada.
Hendler, S.S. (1990) The Doctors' Vitamin and Mineral EncYcloPedia. Simon &
Schuster: New York, N.Y.
Lapin, I.P. (1991) Kynurenines and seizures. EPilePsia 22, 257-265.
Leonard, T.K., Watson, R.R. & Mohs, M.E. (1987) The effects of caffeine on various body systems: a review. Journal of the American Dietetic Association 87, 1048-1053.
Pearce, J.M.S. (1992) Sumatriptan: efficacy and contribution to migraine me~h~n; ~. Journal of Neurolo~Y. Neurosur~erY. and PsYchiatrY 55, 1103-1105.
Stern, R.H., Spence, D., Freeman, D.J., Parbtani, A. (1991) Tolerance to nicotinic acid flushing. Clinical Pharmacolo~Y and TheraPeutics 50, 66-70.
Claims (3)
1. The use of a novel composition for alleviating migraine headaches, consisting of:
100 milligrams vitamin B3 niacin;
500 milligrams calcium carbonate;
64 milligrams caffeine, or up to 100 milligrams caffeine;
650 milligrams acetylsalicylic acid;
500 milligrams or 1 gram amino acid L-tryptophan;
all in a pharmacologically-acceptable state of purity;
taken orally with 120 millilitres of milk when one realizes one has a migraine or awakes with a migraine; that can be repeated four hours later if migraine symptoms return, up to two repeats; once taken, high-potassium foods are to be avoided for several hours; and the standard practice of avoiding intake of hot liquids in the hour after taking niacin applies.
100 milligrams vitamin B3 niacin;
500 milligrams calcium carbonate;
64 milligrams caffeine, or up to 100 milligrams caffeine;
650 milligrams acetylsalicylic acid;
500 milligrams or 1 gram amino acid L-tryptophan;
all in a pharmacologically-acceptable state of purity;
taken orally with 120 millilitres of milk when one realizes one has a migraine or awakes with a migraine; that can be repeated four hours later if migraine symptoms return, up to two repeats; once taken, high-potassium foods are to be avoided for several hours; and the standard practice of avoiding intake of hot liquids in the hour after taking niacin applies.
2. The use of a subcombination of the novel composition, as claimed in claim 1, consisting of all agents minus the L-tryptophan, for alleviating migraine symptoms to a lesser degree than the combination of all five agents.
3. The novel composition, as claimed in claim 1, plus a histamine type 1 receptor antagonist such as a 12-hour non-sedating antihistamine, for alleviating migraines not responding to the novel composition alone, particularly during pollen season, air travel or rapid barometric pressure changes.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA 2127573 CA2127573A1 (en) | 1994-07-07 | 1994-07-07 | Vasotonic treatment for migraines |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA 2127573 CA2127573A1 (en) | 1994-07-07 | 1994-07-07 | Vasotonic treatment for migraines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2127573A1 true CA2127573A1 (en) | 1996-01-08 |
Family
ID=4153966
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2127573 Abandoned CA2127573A1 (en) | 1994-07-07 | 1994-07-07 | Vasotonic treatment for migraines |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2127573A1 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1146879A1 (en) * | 1998-12-08 | 2001-10-24 | The Rockefeller University | Methods and compositions for prevention and treatment of restenosis with non-steroidal anti-inflammatory drugs |
| WO2005102321A1 (en) | 2004-04-19 | 2005-11-03 | Kirin Beer Kabushiki Kaisha | Composition for acceleration of alcohol metabolism or recuperation from fatigue through gluconeogenesis |
| WO2006024545A1 (en) * | 2004-09-03 | 2006-03-09 | Stichting Voor De Technische Wetenschappen | Fused bicyclic natural compounds and their use as inhibitors of parp and parp-mediated inflammatory processes |
| WO2012103377A1 (en) * | 2011-01-26 | 2012-08-02 | Nico Worldwide, Inc. | Remedy for migraine headache |
-
1994
- 1994-07-07 CA CA 2127573 patent/CA2127573A1/en not_active Abandoned
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1146879A1 (en) * | 1998-12-08 | 2001-10-24 | The Rockefeller University | Methods and compositions for prevention and treatment of restenosis with non-steroidal anti-inflammatory drugs |
| EP1146879A4 (en) * | 1998-12-08 | 2002-07-03 | Univ Rockefeller | Methods and compositions for prevention and treatment of restenosis with non-steroidal anti-inflammatory drugs |
| US6620853B1 (en) | 1998-12-08 | 2003-09-16 | Mount Sinai School Of Medicine | Methods and compositions for prevention and treatment of restenosis with non-steroidal anti-inflammatory drugs |
| WO2005102321A1 (en) | 2004-04-19 | 2005-11-03 | Kirin Beer Kabushiki Kaisha | Composition for acceleration of alcohol metabolism or recuperation from fatigue through gluconeogenesis |
| EP1757289A1 (en) * | 2004-04-19 | 2007-02-28 | Kirin Beer Kabushiki Kaisha | Composition for acceleration of alcohol metabolism or recuperation from fatigue through gluconeogenesis |
| EP1757289A4 (en) * | 2004-04-19 | 2007-08-08 | Kirin Brewery | Composition for acceleration of alcohol metabolism or recuperation from fatigue through gluconeogenesis |
| CN1968691B (en) * | 2004-04-19 | 2010-12-29 | 麒麟麦酒株式会社 | Composition for acceleration of alcohol metabolism or recuperation from fatigue through gluconeogenesis |
| WO2006024545A1 (en) * | 2004-09-03 | 2006-03-09 | Stichting Voor De Technische Wetenschappen | Fused bicyclic natural compounds and their use as inhibitors of parp and parp-mediated inflammatory processes |
| WO2012103377A1 (en) * | 2011-01-26 | 2012-08-02 | Nico Worldwide, Inc. | Remedy for migraine headache |
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