JPS61501570A - Methods for altering amine oxidation rates in vertebrates and other organisms - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] Methods for altering amine oxidation rates in vertebrates and other organisms Background of the invention 1. field of invention The present invention can be used to keep the relative abundance of circulating amines within normal limits. Concerning compounds that can.

The present invention increases the inhibition of oxidation of amines and thus The aim is to provide a preparation that provides a relatively high concentration of min.

Furthermore, the present invention prevents inhibition of amine oxidation, continuously destroys amines, As a result, it is directed to providing preparations for relatively low concentrations of the amine in the circulation. Compounds that can be ingested and that affect the rate of oxidation of amines are widely used. It is used. However, these compounds may be affected by factors that occur in the regulatory mechanism. They do not develop their effects as directly as they do. What is currently used Quality may have side effects that interfere with the desired effect, and in some cases can be life-threatening or increases mortality.

Prior art compounds used to accelerate or slow amine oxidation are The same existing metabolic pathways that control naturally produced substances Noamine oxidase converts neuroactive amines to inactive aldehydes It is a flavoprotein oxidase that is thought to be important in central nervous system metabolism. ...Monoamines bound to flavins are present in the outer mitochondrial membrane of animal cells. exists inside. Forsch (Walsb), pages 402 and 403.

Action: Monoamine oxidase is a complex enzyme system that is widely distributed throughout the body.

Drugs that inhibit monoamine oxidase in the laboratory have shown numerous clinical effects. It is related to 1tAO inhibition is responsible for the observed clinical effects Is it the agent itself, other pharmacological effects, or an interaction between the two? is unknown. Therefore, physicians should be aware of all possible effects caused by this class of medicines. must be familiar with.

PDRC Fisheries Desk Reference (Pbysicans’Des k Reference) 1983: ] 11516 pages Two classifications of amine oxidases were published in 1959. Swing (Bla) , 5bkO), etc., to distinguish the activity of various amine oxidases. The response to calenyl inhibitor was used for Zeller et al. A semicarbazide inhibitor was used.

The use of inhibitors to classify amine oxidases is a Difficulties in fabrication and in studying the structure of these active sites are encountered.

80 The presence of monoamine oxidase (tAO) was found in all of the tested animals. Two mammals, birds, reptiles, amphibians and sclerophytes were detected in the class (1970). Osteichthyes (161). This enzyme is found in a variety of different tissues, especially glands, smooth muscle, and nerves. system (162).

In humans, the parotid gland and mandibular line appear to be the most abundant sites for MAO (163) . In response, ○ is also present in molluscs and plants (4). Kabeler-Adler ( Kapeller Adler) 31゜Introduced in 1957 for the treatment of depression. Nyazod was introduced. New York Times article June 4, 1981, page 89 . This drug has been widely studied and is a monoamine inhibitor. However, this drug The product has various effects in addition to its effect on depression. These often cause problems. Rub. These drugs continue to be used experimentally. Ibroniazid is extremely It was removed from the market due to severe liver toxicity. These medicines may be used after starting treatment. It would be interesting to see that they exert their beneficial effects on patients with depression anywhere in the range of ~ few weeks. That's true. In some cases, the reduction in disease progresses to a determined, mildly ill, or even persistently ill state. go This drug causes central nervous system stimulation in normal individuals as well as in patients with depression. You can see the action. Beyan. Other effects include orthostatic hypotension. hypothermia, allergic reactions affecting the liver, dizziness and some anticholinergic drugs There is a type characteristic.

Monoamine oxidase chemistry specificity The specificity of this enzyme, isolated from several sources, is low.

Generally, primary, secondary and tertiary amines, tryptamine derivatives and catechola Min is oxidized (1.5).

However, this enzyme isolated from human placenta only acts on primary amines and is a simple Alkylamines increase chain length and thus increase affinity (7). barman (Barman i page 80).

``Inhibition of MAO affects the concentration of norepinephrine in the sympathetic nervous system and Serotonin, a monoamine in monoamine-containing nerve cells of the nervous system (CNS) very significantly increases the concentration of norepinephrine, norepinephrine and dopamine.・・・ ...Therefore, large amounts of amines accumulate in the cytoplasm. Storage sites are rapidly transmitted The capacity is filled with things. MA is caused by an increase in the accumulation of neuroamines within neurons. ○It is thought to be the basis of the antidepressant effect of inhibitors. ······urine The presence of large amounts of unmetabolized serotonin and 3-0-methylated tedoforamine in It must be added that this is a characteristic of patients who respond to MAO inhibitor antidepressants. I don't want it.'' BeVan, 183.184 pages.

These urinary compounds exhibit clearance with the above amines from the blood, and each amine This corresponds to the rate of increase in the amount of increase in force.

``7-rabin protein (monoprotein) involved in oxidative deamination of catecholamines. Amine oxidase) is found in a wide range of tissues, primarily mitochondrial present in the adventitia of Frisell, 628 pages.

Halogenated compounds often enter the body from the environment.

The anesthetics halothane and methoxyflurane are examples of this.

“A volatile general anesthetic using liver microsomes, NADPH and oxygen Extensive dechlorination when incubated in rotane and methoxyflurane (labeled 1601) transformation occurs. ” “Similarly, thyroxine and triiodotrixine are (8). J Bank (Bacq) 577 pages.

Dimino and Hocb (1972) found that the liver mitochondria of rats injected with I put it out. These midcon F IJs are denser and less fertile than those of untreated animals. The element appeared to be tightly bound to the mitochondrial inner membrane (9)... Direct effects of T4 on isolated mitochondria were known; They occur at extremely high, non-physiological concentrations, and their significance is questionable. (9) Lassi (La5h), 632 pages.

``The actual biochemical mechanism of thyroid hormone's effect on neural tissues is largely unknown. "It's great."

``It is clear that there is no sheep-like regulatory response that can explain the diverse effects of thyroid hormones.'' ”.

“It has been shown that the activity of more than 100 enzymes is affected by thyroxine administration. however, these enzymes do not appear to be affected to the same extent (10).

” Norinocell (Frisell), p. 608.

manganese metabolism Greenberg using radioactive manganese (65) Early studies showed that only 3-4% of an oral dose was absorbed in rats. is shown. Absorbed manganese rapidly appears in the bile and in the feces. was discharged. From that point on, experiments on several species including humans revealed that man It has been shown that cancer is almost entirely eliminated from the intestinal wall by several routes. . These pathways provide effective homeostatic mechanisms by which the body regulates manganese concentrations in tissues. They are interdependent and combined so that they can be maintained (16.90.129). initial The relatively stable concentration of manganese in tissues shown in the literature suggests that This is due to the regulation of emissions rather than the control of intake. (27).

Underwood, 184 pages.

Each of these tissues in the intestinal tract is actually the same system for absorbing and excreting manganese. It should be understood that you are using This is true in the mitochondria mentioned above. It is the same flow as a man who enters and exits again. This is very scary This is due to the influence of the accumulation of Midocon F 1.1A, which is an easy accumulation. Manganese is protoplasm transported inside and combined with proteins. Very little manganese is removed by the kidneys. Ru.

Injected radioactive manganese rapidly disappears from the bloodstream (23.90). Polk (Borg) and Cotzias (28) have shown that this removal was divided into three stages. The first and most rapid of these steps is via the regular capillaries. The removal rate of other small ions considered to be The effect is the same as that of immersion food. Therefore, calcium retains absorbed manganese. as well as affecting Manogaf metabolism by affecting the absorption of manganese. It seems so.

Changes in phosphorus due to diet are comparable to the excretion of 54MH administered intrathecally. , but the absorption of orally administered 54Mn is inhibited. under Wood 186 pages.

In the 1970s, an ill-advised book appeared on the structure and transport of mitochondrial membranes. and brought energetic attention to change. In contrast, mitochondria Phosphate oxidation by oxidation of a was devised, and the modification was made to great acclaim. In 1975 , the claim that many solutes can cross the mitochondrial membrane without active transport. Therefore, some of the above theories were abandoned. Regarding these transfers, protons, A number of hypotheses have been proposed, including phosphate and other mechanisms.

In muscle and nerve tissue, the Q between the inner and outer surfaces of the cell membrane is mV or There is a greater difference than that.

Various data can be explained using the Ca/Mg pump.

Highly resonant phosphate compounds that activate mitochondrial cation pumps Looks like good data. Such a pump depends on the calcium concentration. and is also regulated by magnesium. Mn is mitcon You can easily enter and exit Doria.

It acts in conjunction with active transport and alkaline earth metal cations. other metals is also involved, but to a small extent. Na/K ATPase pump and tandem (Tandem) operated Ca/Mg pumps only fit into the cell membrane. rather, it occupies a place in the mitochondrial structure.

,? ) Chondria are primitive cells that were originally ingested when the cell's phagocytic function developed. It has long been proposed that it is a fungus. The effective oxidation method of ingested cells is the symbiotic explained as the cause of development. A natural consequence of such a proposal is that the original cell and It is necessary to develop a correlated flow of highly resonant compounds between tochondria. this theory Then, metabolic diseases occur at the site that makes complex metabolic adjustments between the metabolism of these two different types of cells. suggests that this will naturally occur. This mechanism of regulation is consistent with the above theory.

The high efficiency of mitochondria as a source of highly resonant coupling makes it necessary for a central control mechanism. I must add that it emphasizes the importance of this. The simple mechanism is Mitoko Energy metabolism in Ndria and energy metabolism in cells, organs, and indeed the whole organism must be compared.

Calcium is a modulator of the interaction system between eukaryotic cells and mitochondria. It seems like an inevitable choice for a writer. This is consistent with the above interpretation. stomach.

This control mechanism or system was called the coordination mechanism.

In order, the explained components are cations, ATPase pumps, gnats, and gnats. amines, thyroid hormones, monoamine oxidases and amines. these are It has been discovered that all of these have a close relationship with mitochondria [mania] ,...is certainly one of the most histrionic of all mental illnesses. . Within a few days or weeks, a rational, high-temperature individual becomes uncontrollably frenzied.

The mildest form of the disease, cowardice, involves whether the patient is mentally ill or his work. In fact, it is important to determine whether the individual is behaving in an idiosyncratic manner simply because of some change in the family environment. difficult to understand: often some unusual event has a disproportionate influence It is possible.

First, the patient usually attracts more people's attention. The course of daily life is suddenly disrupted be done. Facial expressions become more happy and active; clothing becomes less restrained and slightly more erratic. It's off track. All movements and reactions become more and more active.”

``Acute cowardice is a severe degree of cowardice.

At this stage the patient's behavior is undoubtedly abnormal...''

"In hyperacute cowardice or delirium cowardice, the patient is completely unable to control himself. He lies on the floor. Constantly struggles and writhes when stopped. The way he speaks is completely incoherent. Shi, what you say doesn't mean anything.''

This is typical cowardice. The patient is a typical chronically ill patient. The patient has recurrent depression and mental illness. He is a patient with a divine illness. This disease is also caused by cowardice and depression in this patient. Also called bipolar psychosis. It is said that depression is ten times more common than cowardice. very In extreme cases, patients drift in and out of depression. In other cases, 11 has an intermediate onset of cowardice. Responsible for the work. In the middle, they move back and forth from one pillar to the other.

Other illnesses include mental and functional advances in the brain, splitting, disorientation, delirium and sometimes is cowardice combined with death. Many of our patients receive a ``thyroid cry'' from their surgeon. risj, s) J or "Thyroid Storm" The patient dies on the operating table before the gland can be removed.

Severe thyrotoxicosis is the patient's diagnosis.

Some miners in Chile contract chemotaxis. If they are simply an alcoholic, It will be called Running Jag (running Ja, g) J. he etc. do not know why they run or engage in other intramuscularly stimulating behaviors. Mine is mambo Due to frequent incidents of cowardice in the mine, the mine had to be closed. Cotchias (Cot) Zias) researched this disease and found that miners with low Mn in their bodies are dangerous. I found it. This means that miners who have a relatively large amount of blood but are not cowardly This seems to be due to the inability to quickly metabolize intuition.

The above six types of timidity are commonly explained in the explanation before this supplement to the prior art, Section ①. It has an alteration of the "CMTA sequence" as described above.

After all, miners believe that after Mn activity is consumed within cells, neurological deficits are expected. It wasn't as bad as it was. These miners suffer from respiratory and oral were taking in manganese. Monoamine oxidase is inhibited in the explanation section above. The presence of excess amounts of all types of amines, especially catecholamines, when and discussed it. In hyperthyroidism, increased concentrations of catecholamines It has been reported in the literature that T4 and Increased amounts of Mn and T3 emphasize the involvement of Mn in certain thyroid diseases. ing. In these three types of timidity, catecholamines, serotonin and other The sudden increase in amines causes a feeling of increased strength, greater vitality, and an enormous impact on the patient. It caused a lot of confusion. This made him recurrently ill. This is typical madness This is the cause.

Ray Adams is a member of Harrison Spring Sol Og International Medicine (Harrison's Prj, ncip) Le of International Medicine) 1970 No. 6 In his discussion on pages 1871-1874 of the edition, the causes and mechanisms of disease, i.e. A brief commentary on depressive psychosis. The role of genetics, body type and personality psychology Correlations with academic structure, obsessive-compulsive tendencies, and other traits that are thought to be correlated I am commenting.

Endocrine disorders were attempted to be the vehicle by which genes change their functions, but without success. deer However, recently, with the discovery of the antidepressant ibroniazod, monoamide Increases the amount of epinephrine in the brain by inhibiting epinephrine oxidase, and increases the amount of epinephrine in the brain Pramine (another antidepressant) has similar effects by other mechanisms, but chemical It gave new impetus to theory. This is because deservin can cause depression. It is capable of antagonizing dopamine, a precursor of catecholamines. It is also on the same line as earlier observations such as what can be done.

As Kezy from our lab did, this evidence suggests that ``the brain is special. Certain biogenic amines, especially catecholamines, present in the The conclusion is that this supports the concept of can be done. Therapeutic agents such as pharmaceuticals and electroconvulsive therapy contain norepinephrine and and possibly increase the effective concentration of other amines in synthesis, release, etc. That's probably why.

CMTA sequences could explain these findings and, more importantly, The thing is that the normal mechanisms that regulate the amounts of the substances that make up all these regulatory mechanisms are be able to explain the structure.

Electric shock therapy is a frightening experience. This disrupts structure and function, memory defects gradually disappear.

It takes several weeks or months. However, these disappearances are due to the silkworm white matter structure of the central nervous system. This is proof that the structure remains intact. Neurotransmitter stores are disturbed.

Lithium salts are gradually reduced to a timid state. of emotion, vitality and attention span. The change is proportional to serum lithium concentration. “Toxic concentrations of lithium are close to therapeutic concentrations. Suru J PDR1198337 edition 19o4 pages. 1 to 3 weeks to suppress acute symptoms It takes. “Kidney disease can be caused by excessive concentrations and toxicity. Lithium There is no known antidote to the poison." Said document.

Lithium salts have long been used in the treatment of depression. This was 30 years ago or so. It was used by Australian doctors and was widespread in psychiatry even before that time.

The first use of lithium salts was probably ancient? It is thought that it was Risha or earlier. Ru. In Greece, springs and convulsions were associated with oracles. Even today in Europe , some springs are probably associated with certain diseases.

There are many theories and explanations for the use of lithium. Most of the When tested using related biochemistry, they do not come together. If I could explain it, Richiu is the size of the radius of the circle. This element is below hydrogen in the first column. Its atomic number is It is 3. Its atomic weight is approximately 7.

single bond covalent valence Radium is 1.23; Metal 1.55 Sodium 1.54 1.90 Potassium 2.03 2.38 Demitras, etc., In-O's Nick Chemistry -(Inorganic Cbemi#try) Table 2・1 Page 34 1 972° The sodium/potassium ATPase membrane pump is located inside muscle cells or nerve cells. and maintain a charge difference between the outside of these cells. sodium is pumped out It is said that potassium then enters the body. The pump action is a monovalent ion. Richi Monovalent ions of um are in a size range comparable to sodium. More closely matched The ionic radius of the hydrated form is not given. Lithium is probably the pump mentioned above. The effect may be slow.

Summary of the invention Manganese to slow down the oxidation rate of amines and thereby increase the amine concentration. Cancer-containing preparations are indicated by changes in basal metabolic rate (BMR) and emotional tension. produce high levels of physiological activity.

Group 1 IA to promote the oxidation of amines and thus reduce the concentration of amines. calcium-, magnesium- and strontium-containing compounds; Group zinc-containing compounds; Group 1B copper-containing compounds; and Group ffB iron-containing compounds. The divalent cationic composition of is indicated by changes in BMR and emotional tension. Produces low levels of physiological activity.

According to the present invention, it is suitable for use in the system of oxidation of amines in salivary mammals and plants. An elemental compound is provided. Combining these elements to control amine oxidation rates It is the general concept of the invention to provide an object.

In particular, the compositions of the present specification are suitable for Group IIA, Group IB, Group νIB and Group IIA. Concerning alkaline earth metals and transition metals of the UB group. Furthermore, said composition using said elements in proportions that are compatible with the elements in vertebrates and other organisms.

That is, in Group 1IA, calcium, magnesium and strontium are use.

Group 1IB uses manganese.

In Group 1, iron can be used if permitted.

In Group 1B, copper can be used.

Group JIB uses zinc.

i.e. calcium, magnesium, strontium, manganese, iron, copper, and zinc in proportions that are compatible with these metals in vertebrates and other organisms.

Trace elements found in mammals in general and humans in particular are influenced by genetic factors.

The following examples are provided for further understanding of the present invention, but are for illustrative purposes only. Ashi provides details of the formulations of the present invention and the clinical results obtained with such formulations. vinegar.

There were no timid patients.

The large number of patients who took manganese-containing preparations included those with a wide range of common illnesses. Ta. A commonly used compound was manganese gluconate. using pure substances emphasize that. In each case, the amount of manganese gluconate used was The required amount was measured. Manganese has been dispensed or sold to patients for several years. contained in a mixture with other nutrients and traces of minerals. such preparation What is remarkable is that different patients have different predominant effects, and some patients have different effects than others. The action that can be seen is far greater, and the opposite is true.

Formulations containing traces of three minerals and two amino acids show that these inconsistencies are evident. He was an author. It is clear that no correct conclusions can be drawn using such preparations. It was clear. In each case, the trace metals to be studied had to be done in isolation. .

Research began using one of the other transition metals. This study selects the effect It took a very long time.

Once I had a thorough understanding of these, I began research on manganese. This surprised me from the beginning What should be done has been proven.

Example 1 Patients A, H.

Type ■ Period of chronic muscle tension in diabetes and essential hypertension Treatment period: daily to every 1 to 3 weeks Treatment: Periodic collection of fasting blood sugar (70% of the time) Hypoglycemic agents were administered in 80% of cases.

Antihypertensive drugs were administered at 7D% of the time.

Manganese gluconate was administered 30% of the time at doses ranging from 2 to 6 m9 during testing. Ta.

Blood sugar = (90-100) ~ (170-180)■/100m and changes, Usually it varied from 100 to 150.

Blood pressure: changed from 130/82 to 184/80 nm+Hg.

The contraction pressure changed from 130 to 184.

The expansion pressure varied from 70 to 90.

Pulse rate changed from 68 to 92.

Pulse pressure: (=systolic pressure - diastolic pressure) varied from 48 to 106 unag.

Drug treatment ratio: Hypoglycemic agent 2.5/e - 60/e depending on the change, total administration Measure the amount in m9. The dose of hypoglycemic agents varied from 50 to 1500.

When used together, the minimum ratio of hypoglycemic agent to manganese is 17/1 to 100/1. .

The highest ratios of blood thinner:manganese ranged from 167/1 to 750/1.

The duration of treatment for manganese varied from daily to two weeks or more.

Clinical response Two muscle tone gradually improved.

High glucose levels appeared in conjunction with pain recollections and sleep deprivation.

80% of fasting blood sugar level decreased to 100-150m9/100ml.

Example 2 Patient: E, G, late middle age The second half of the early stage (type ■)! Stress phase of urinary disease NIDDM treatment period: daily ~4~5 every day Treatment: At the time of fasting blood sugar collection and testing, administer hypoglycemic agents every morning with manganese gluconate 6-2 5 da/dose was administered at the time of treatment.

Blood sugar: Changed from 175m9% to 120% over a period of 6 weeks.

Purpose of treatment: To restore blood sugar levels to an acceptable range of 110-140 η%.

Clinical response: Sensitive to blood sugar levels regardless of concentration.

The patient is essentially asymptomatic ? Occult Infection.

(occult 1nfection) Example 3 Patient: BJ:, middle-aged A history of recurrent episodes of depression. The stress period is caused by a rather long period of relapse.

Treatment period: Sometimes during depression because due to circumstances I cannot come every day. other drugs Treatment is possible daily.

Treatment: Assessment of emotional state. Dietary therapy to stabilize blood sugar.

After the first treatment using antidepressants and manganese gluconate, about 4 m9 The dose was calculated as η of Mn in gluconate, which was determined to be ~8m9).

Treatment period: every 2-3 days from the first day. Continue this treatment for 10-14 days and then , every 3-4 days for 1-2 weeks or more, then suddenly once a week for 10-1 Once every 4 days, then once every 3-4 weeks.

Dietary therapy was sufficient for 1-2 months.

Aim of treatment: To restore emotional tone to normal range.

Clinical response: Normal emotions and emotional patterns are observed over 3 weeks using the complete study design. However, the normal pattern of response was delayed for 6 to 8 weeks. Provide auxiliary treatment while waiting Ta.

Second experience: I went there for a very short time. After about 1 week of treatment as above, the same level of improvement was achieved. was gotten. Then 8-12m20Mn as gluconate and large doses of Antidepressants were administered at weekly or longer intervals. Rapid improvement was seen . continued for the entire design of the study.

Scope of drug treatment: A maximum of 8m9 Mn was required. This range: The distance between them was quickly shortened. - Once the reaction pattern is known, the plan can be accelerated. was completed.

In the example above, the same ratio of cancer and other therapeutic agents used This proves that there is no hope in symptomatic diseases.

Cowards are not given manganese. This purpose is to establish a negative manganese balance It's for a reason.

During depression, patients were administered 5-10/75 kg of manganese.

During hypertension, initially from 5-12.5 m9/75 kg or more to 25-12.5 m9/75 kg or more 50m9/751; ie, the highest concentration was reached early in the treatment. Next Then, the amount is gradually reduced and gradually becomes occasional.

For diabetes, 6~5・n9150 yu~12.5~25■150 yu or more It is characterized by the dosage of

Hypertensive patients require 5m9150kg or more at the beginning of treatment. .

At the same time that manganese absorption changes, anticowardice drugs, antidepressants, antihypertensive drugs, antisugar Dosages of urinary medicines and antiglycemic drugs also vary. As a result, the therapeutic ratio is It is characterized by fluctuations.

Calculate the recommended amount of manganese as gluconate (value indicated by Manganese 9), then show: Recurrent disease 0 or negative (balance) amount Depression 1m9=100On,? (Nonagram), 76-133 ng/kg body Heavy.

Hypertension 67-333 n,! ? /hot water.

Diabetes 100-500n? /m (i.e. 0.1~0.5 rrL?/ kg).

Hypoglycemia 0.1 m9/-9 or more can be used initially.

The general nature of manganese's effects is similar to that of hypoglycemia and hyperglycemia in diabetes. This is evidenced by the fact that it can be administered to the syndrome that is the opposite.

Changes in the intestinal excretion of manganese appear when large doses are administered.

This makes it easier for clinicians to predict the effects of a given dose of manganese. This can be best avoided by doing what you can. In addition to such adjustments, cumulative treatment This is necessary when changing dosage levels in a project.

The condition of the treated disease is such that it is no longer life-threatening, even if at least some degree of mortality has been avoided. of the interaction between energy and the underlying metabolic cycle that is unable to maintain vitality. This is the result. On the one hand, there are no clear indications of the metabolic cycle on the other hand. Sunawa Aches, pains, and stiffness, such as can be seen when an old dog stands up, can occur throughout the individual's life. An accumulation of ankylosis-like complaints appears.

Submission of translation of written amendment (Article 184-7, Section 1 of the Patent Act)

Claims (2)

[Claims] (1) A method for changing the oxidation rate of amines in vertebrates and other living organisms, the method comprising: , (a) low levels of compounds containing calcium, magnesium, strontium and zinc; an effective non-lethal dose of at least one; (b) an effective non-lethal amount of a preparation consisting essentially of a manganese compound; orally to said subject in a ratio effective to alter the rate of oxidation of the amine. The above-mentioned method, characterized in that: (2) (a) Compounds containing calcium, magnesium, strontium and zinc an effective non-lethal amount of at least one of (b) an effective non-lethal amount of a preparation consisting essentially of a manganese compound; and to the affected subject in a ratio effective to alter the rate of amino oxidation. A method for changing the oxidation rate of amines in mania, characterized by: