WO1985003867A1 - Procede de modification de la vitesse d'oxydation d'amines dans les vertebres et d'autres organismes - Google Patents

Procede de modification de la vitesse d'oxydation d'amines dans les vertebres et d'autres organismes Download PDF

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Publication number
WO1985003867A1
WO1985003867A1 PCT/US1985/000329 US8500329W WO8503867A1 WO 1985003867 A1 WO1985003867 A1 WO 1985003867A1 US 8500329 W US8500329 W US 8500329W WO 8503867 A1 WO8503867 A1 WO 8503867A1
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WIPO (PCT)
Prior art keywords
amines
manganese
oxidation
rate
vertebrates
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Application number
PCT/US1985/000329
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English (en)
Inventor
Vernon Erk
Original Assignee
Vernon Erk
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Vernon Erk filed Critical Vernon Erk
Publication of WO1985003867A1 publication Critical patent/WO1985003867A1/fr

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    • 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
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/32—Manganese; Compounds thereof

Definitions

  • This invention relates to changing the rate of oxidation of amines in vertebrates and other organisms. It relates to the relative abundance of circulating amines. It relates to the compounds which can be used to keep the relative abundance of circulating amines within normal limits.
  • the invention is directed to providing preparations that will increase inhibition of the oxidation of amines and thereby permit larger concentrations of said amines in the circulation.
  • the invention is directed to providing preparations for the prevention of inhibition of the oxidation of amines and thus permitting continued destruction of the amines which results in smaller concentrations of the said amines in the circulation.
  • “Monoamine oxidase is a flavoprotein oxidase of purported CENTRAL METABOLIC IMPORTANCE CONVERTING NEUROACTIVE AMINES INTO INACTIVE ALDEHYDES....
  • the flavin linked monoamine oxidase is localized in the OUTER MITOCHONDRIAL MEMBRANE OF ANIMAL CELLS. Walsh pp. 402, 403.
  • Monoamine oxidase is a complex enzyme system widely distributed throughout the body. Drugs that inhibit monoamine oxidase in the laboratory are associated with a number of clinical effects. Thus, it is UNKNOWN WHETHER MAO INHIBITOR PER SE, OTHER PHARMACOLOGICAL ACTIONS, OR AN INTERACTION OF BOTH IS responsible for the clinical effects observed. Therefore, the physician should become familiar with all the effects produced by drugs in this class. PDR (Physicians' Desk Reference 1983) p. 1516.
  • MAO Monoamine oxidase
  • the enzyme isolated from a number of sources exhibits low specificity. In general, primary, secondary, and tertiary amines, tryptamine derivatives and catecholamines are oxidized (1,5). The enzyme isolated from human placenta, however, will only attack primary amines and with simple alkyl amines increase in chain length results in increased affinity (7).” Barman p. 180.
  • Halogenated compounds enter the body frequently from the environment.
  • the anaesthetics halothane and methoxyflurane are cases in point.
  • a Ca/Mg pump explains a wide variety of data. There seemed initially to be good data for high resonant phosphate compounds activating the cation pumps of mitochondria. Such a pump is affected by changes in concentration of calcium and it is also modulated by magnesium. Mn goes in and out of mitochondria readily. It dose so by active translocation and in the company of alkaline earth metal cations. Other metals participate but to a lesser degree.
  • a Ca/Mg pump operating in tandem with Na/K ATPase pumps not only fits the cell membrane, but it also would have a place in the mitochondrial scheme of things.
  • the patient is the classic maniac.
  • the patient is manic-depressive, psychotic.
  • the disease is also called dipolar psychosis because of the tendency for such patients to have both mania and depression.
  • Depression is said to be ten times as common as mania. At one extreme patients drift in and out of depression. At the other, patients have intermittent bouts of mania. In between are those that swing back and forth from one pole to the other.
  • the CMTA sequence explains these observations and more importantly explains the normal mechanisms for controlling the amounts of the substances making up the mechanism of regulation of all of this.
  • Electroshock is a terror-producing experience. It
  • Lithium salts gradually slow down the manic phase. Alterations in affect and activity and attention span correlate with serum lithium levels, "The toxic levels for lithium are close to therapeutic levels.” PDR, 1983 37th edition p. 1904. One to three weeks are required to gain control of the acute manic phase. Renal disease may contribute to excessive levels and toxicity. "No specific antidote for lithium poisoning is known.” Ibid.
  • the use of lithium salts has long been employed for the treatment of manic-depressive psychosis. It was revived three decades or so ago by an Australian physician and was popularized in psychiatry. The original use of it was probably in ancient Greece or earlier. In Greece, springs and spas were associated with the oracles. As in Europe today, certain springs probably became associated with certain diseases.
  • lithium has a number of explanations provided for it. For the most part these do not hold together well when examined in terms of the biochemistry involved. The probable explanation is in the size of the radius of the lithium.
  • the element is below hydrogen in the first column. Its atomic number is three. Its atomic weight is about seven.
  • the single bond covalent radium is listed as 1.23; the metallic as 1.55, For sodium and potassium the values are:1.54 and 1.90 and
  • the sodium/potassium ATPase membrane pump is responsible for maintaining the difference in charge between the inside of the muscle cell or the nerve cell and the outside of each of these cell-types.
  • the sodium is pumped out, the potassium is said to fall in.
  • the pumping is of the monovalent ions.
  • the monovalent ion of lithium is of the competitive size range with the sodium.
  • the ionic radii are not given for the hydrated forms of these which may match more closely. Lithium would have a slowing effect upon the pump.
  • compositions of the subject Patent Application deal with the alkaline earth metals and transition metals found in Groups IIA, VIIB, VIIIB and
  • compositions utilize the elements in the ratios compatible with those in vertebrates and other organisms.
  • Group IIA utilizes calcium, magnesium and strontium.
  • Group VIIB utilizes manganese.
  • Group VIIIB may utilize iron if it is well-tolerated.
  • Group IB may utilize copper.
  • Group IIB utilizes zinc.
  • calcium, magnesium, strontium, manganese, iron, copper and zinc are utilized in ratios compatible with those in vertebrates and other organisms.
  • the numbers of patients taking the manganese-containing pharmaceutical preparation included a wide range of common diseases.
  • the compound commonly used was manganese gluconate. The emphasis was upon the use of pure substances. In each case the amount of the manganese gluconate used was determined at the time of use in terms of the amount required.
  • Treatment Periods daily to one to three week intervals. Treatment: Fasting blood sugar drawn periodically
  • Blood glucose varied from(90-100) to (170-180) mg/100ml, usually from(100)to(150).
  • Blood pressure varied from 130/82 to 184/80 mm. of mercury.
  • Systolic pressure varied from 130 to 184.
  • Diastolic pressure varied from 70 to 90.
  • Pulse varied from 68 to 92.
  • Medication ratios As between hypoglycemic agents varied from
  • hypoglycemic agent with the lowest ratio to manganese ranged from 17/1 to 100/1 when given concurently.
  • hypoglycemic agent with the highest ratio to manganese ranged from 167/1 to 750/1.
  • Treatment intervals for Mn varied from daily to 2 weeks or more.
  • Treatment Periods daily to every 4 to 5 days.
  • Blood sugar varied from 175 mg% to 120 mg% over six week interval.
  • Objective of treatment to restore blood sugar to normal range with 110 to 140 mg% acceptable.
  • Treatment periods Circumstances prevented daily visits during depression on one occasion. On another daily medication possible.
  • Treatment Evaluation of emotional status. Dietary management for stabilization of blood sugar.
  • Treatment Period Interval Initially daily to every two- three days. This continued for ten to fourteen days, then, every three to four days for a week or two more, then quickly to once a week, once every ten to fourteen days and then every three to four weeks. Dietary program became sufficient with intervals at one to two months.
  • Clinical Response Normal affect and emotional pattern with full work schedule within to to three weeks, but with normal pattern of response delayed to six to eight weeks. Supportive treatment at intervals.
  • Second episode Very little time for treatment. Followinged as above about one week with same degree of improvement. Then, given 8 to 12 mg manganese as gluconate and large dosage of antidepressant at weekly or longer intervals. Rapid improvement. Continued full schedule of work.
  • Range of medication About eight mg manganese most needed at any one time. This was quickly spaced out and reduced. Once pattern of response known, program could be accelerated. The examples demonstrate that the same ratios of manganese and the other medications used cannot be expected in the various disease states.
  • hypertension may vary from 5. to 12.5 mg/75 kg or more up to 25 to 50 mg/ 75 kg initiallly, i.e., at the top level arrived at early in treatment. The amounts then become smaller and smaller and more and more infrequent.
  • Diabetest mellitus is characterized by doses ranging from 3 to 5 mg/50 kg up to 12.5 to 25 mg/50 kg or even more.
  • hypoglycemia 5 mg/50 kg or more may be needed during the initial phase of treatment.
  • the intake of antimaniacal, anitdepressant, antihypertensive, antidiabetic and antihypoglycemic agents is also varying.
  • the therapeutic ratios may be characterized by constant fluctuations. Calculated recommended amounts of manganese as the gluconate
  • Depression 1 mg 1000 ng (nanograms) 76 to 133 ng/kg body weight.
  • Hypoglycemia 0.1 mg/kg or more may be used in the early stages.
  • the disease states treated result from interactions between the underlying metabolic cycles being no longer able to sustain life and vitality free of at least some degree of morbidity. There is no clear overlay of symptoms on the one hand and the metabolic cycle on the other. Thus, as an individual ages, there develop accumulations of complaints, such as aches and pains and stiffness, e.g., the stiffness apparent when one watches an old dog get up.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Inorganic Chemistry (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)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

L'invention consiste à administrer des préparations pharmaceutiques contenant du manganèse pour réduire la vitesse d'oxydation d'amines, et à administrer des composés pharmaceutiques contenant du calcium, du magnésium, du strontium et du zinc pour accélérer la vitesse d'oxydation d'amines dans les vertébrés et autres organismes et pour traiter les accès de folie.
PCT/US1985/000329 1984-03-01 1985-03-01 Procede de modification de la vitesse d'oxydation d'amines dans les vertebres et d'autres organismes WO1985003867A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US58528984A 1984-03-01 1984-03-01
US585,289 1984-03-01

Publications (1)

Publication Number Publication Date
WO1985003867A1 true WO1985003867A1 (fr) 1985-09-12

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EP (1) EP0174980A4 (fr)
JP (1) JPS61501570A (fr)
AU (1) AU597561B2 (fr)
WO (1) WO1985003867A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4654213A (en) * 1985-09-11 1987-03-31 Cheesebrough-Pond's Inc. Novel anti-microbial systems containing the magnesium sulfate adduct of 2,2'-dithiobis-pyridine-1,1'-dioxide and a water soluble zinc salt

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4041154A (en) * 1975-02-20 1977-08-09 Verla-Pharm Arzneimittel-Fabrik Apotheker H. J. V. Ehrlich Magnesium-containing pharmaceutical compositions
US4337245A (en) * 1980-07-21 1982-06-29 Baisden C Robert Nutrient compound

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HU187467B (en) * 1981-11-02 1986-01-28 Vetoemagtermeltetoe Es Ertekesitoe Vallalat,Hu Method for producing preparation suitable for preventing health deterioration of alimentary origin promoting the utilization of fodder of animals
US4752479A (en) * 1986-05-27 1988-06-21 Ciba-Geigy Corporaton Multi vitamin and mineral dietary supplement with controlled release bioavailable iron

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4041154A (en) * 1975-02-20 1977-08-09 Verla-Pharm Arzneimittel-Fabrik Apotheker H. J. V. Ehrlich Magnesium-containing pharmaceutical compositions
US4337245A (en) * 1980-07-21 1982-06-29 Baisden C Robert Nutrient compound

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
Chem. - Biol. Interactions, Vol. 37, 1981, MURTHY, Effect of Manganese and Copper Interaction on Behavior and Biogenic Amines in Rats Fed A 10% Casein Diet, pages 299-308 *
CHEMICAL ABSTRACTS, Vol. 90, 1979, SHUKLA, Species Variation in Manganese Induced Changes in Brain Biogenic Amines, Abst. No. 198507v *
CHEMICAL ABSTRACTS, Vol. 99, 1983, CHANDRA, Psychiatric Illness Due to Manganese Poisoning, Abst. No. 100473u *
European Journal of Pharmacology, 71, 1981, DETH, Inhibition of alpha-Receptor-Induced Ca2+ Release and Ca 2+ Influx by Mn2+ and La 3+, pages 1-11 *
Neurology, Vol. 17, 1967, MENA, Chronic Manganese Poisoning, pages 128-136 *

Also Published As

Publication number Publication date
EP0174980A1 (fr) 1986-03-26
AU597561B2 (en) 1990-06-07
EP0174980A4 (fr) 1987-10-08
JPS61501570A (ja) 1986-07-31
AU4110885A (en) 1985-09-24

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