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THE DISCOVERY OF THE ANTIDEPRESSIVE SUBSTANCES
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MARIA OF THE PILLAR YAGÜE, R.N.
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THE MELANCHOLIA (DEPRESIÓN) TABLE OF THE PAINTER ALBERTO DURER
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BRAIN AND CEREBRAL BARK
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OUR REPTILE BRAIN: THE SYSTEM LÍMBICO
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DESCRIPCIÓN OF THE DEPRESIÓN BY PLUTARCO
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STATEMENTS OF SICK DISMAL FAMOUS: TOLSTOY
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STATEMENTS OF SICK DISMAL FAMOUS: VIRGINIA WOOLF
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DISMAL SICK OTHERS FAMOUS: ABRAHAM LINCOLN AND WISTON CHURCHILL
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THE MANIA
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THE DISCOVERY OF THE ANTIDEPRESSANT MEDICINES
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INHIBITORS OF THE AMINOOXIDASAS: IPRONIAZIDAS.
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THE IPRONIAZIDA
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PLAN OF HAPPENED WHAT IS TO THE PREVIOUS MONKEY
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ADMINISTRACIÓN OF IPRONIAZIDA TO THE SAME CUTE DEPRESSED
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PLAN OF HAPPENED WHAT IS WITH THE IPRONIAZIDA
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OTHER ANTIDEPRESSANTS: THE IMIPRAMINA
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MECHANISM OF ACCIÓN OF THE IMIPRAMINA
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HIPÓTESIS TO EXPLAIN THE DEPRESIÓN
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CEREBRAL MAP OF THE RICH NEURONS IN THE TRANSMITTING SEROTONINA AND NORADRENALINA
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The human brain different has parts each one of those which desempañan functions diferentes.Las nervous cells or neurons are organized in circuits that generate and direct messages toward various cerebral fields in a way ordenada.Rodeando to the brain there is a very important field called CEREBRAL BARK that it is where takes place the perception and the pensamineto logical and where is processed the información3necesar for the cerebral functions but complex as the reflexive thought and the report.
Under the cerebral bark exists a very complex field formed by various structures (hipotálamo,hipoca cerebral,núcleo caudado,corteza frontal ...etc) that is designated SYSTEM LÍMBICO.Bajo the point of view of the evolutionary development the SYSTEM LÍMBICO is the part but old and but ancestral of our cerebro.Por that is known to him/her/you also with the name of - " reptile brain " - because serious the cerebral part one homestead of our possible ancestros.El SYSTEM LÍMBICO is the responsible for giving emotional color to the perceptions and thinks that they have been elaborated in the bark cerebral.Este system modula,controla and regular our emociones,sentimie sexual,ritmos biológicos,motiva... .etc
The Greek biographer Plutarco described with great realism and perspicacity to a patient depressed with these words: - " Is sat outside of the gates of the city drawn into the sack fabric or in rags inmundos.Alguna time that other is rolled nude in the mire being accused of have assignment is not known what crimes or lack; ate or drank something that not debia, was carried of a manner that the divinity was not approving. " -
The Lion writer Tolstoy wrote: - " The truth is that the life not teía for me any sentido.Cada gave of my life, each step in her went me approaching edge of a precipice from where would see before me clearly the ruin final.Detenerme or to recede were impossible two; neither could either to close the eyes so as not to to see the suffering that was what is only that was waiting me, the death of all in me, until the annihilation. Thus I, sound and happy man, I was carried to feel that could not live more, than an irresistible force was throwing me to the tomb. " -
The novelist Virginia Woolf as far as he/she is concerned said: - " The thing surprises me? that they are these sudden assaults of total depletion?. I come here to write; can not neither to finish a phrase; am dragged downward; now I am feeling this undefinable impulse: the subconscious deribándome toward their/its/your/his interior?? I have been reading to Faber on Newman; have compared their/its/your/his statement of a nervous depression; the rejection of some part of the mechanism. It is this what to my happens me?? Not exactly. Since I do not am evading me yoúre welcome. No. I Believe that the effort of living two fields; the novel and the life, it is a tension....
However the constant frantic activity of the American President Theodore Roosevelt suggests that this patient was suffering of mania. Because the depression is alone one of the forms with which can be presented clinicamente the calls transtornos affective or of the humor.La other expensive of the currency is the mania. The sick maniacos give sample of an overdone activity, of a waste of energias, of an exaltation and of an overdone optimism. These patients maniacos are returned fanciful, durmen very little, they are always plethoric of energia and often are boarded in expenses and ruinous businesses. Tend mostar a continuous prattle lacing some phrases with other in what is designated - " ideas flight " -. In occasions the transtornos affective is manifistan alone with dismal symptoms (transtorno unipolar) while other times is alternated with symptoms maniacos (transtorno bipolar or psychosis maniacodepresiva).
The depression has been a terrible and devastating enfermedad.Muchos sick depressed have thought in be removed the life and some from they in fact they have been suicidado.La death incidence by suicide in the patients maniaco - dismal is of about 10%. or this through the centuries has been attempted to try the depression with different means. For example these sick have been treated with opium, but the euphoria that this drug produces is very short and on the other hand the patients were worsening of their/its/your/his depression to be made addicted to the opium.
We recall that so that they could be transmitted the nervous impulses from a nervous cell or neuron to to other was necessary the presence of the transmitters (serotonina,noradre ...etc) in the existing space among 2 cells or space sináptico.. We want asi same to recall that the trasnmisores are destroyed by some substances called MAO (Monoaminooxidasas). Now then the first antidepressant that was discovered was ' the IPRONIAZIDA that it is a medicine that inhibits or neutralizes the MAO and by so much to the have not MAO can not be destroyed the transmitters and consiguintemente there will be a greater quantity of available transmitters in the space sináptico, being facilitated the transmission of the nervous stimuli.
In 1956 Nathan Kline employed for the first time the iproniazida in a patient depressed with a spectacular success. This discovery was had to in part at random. The iproniazida was begun to use around the beginning of the years 50 to try to the sick tuberculosos.Al be observed that these sick treated with this medication were euphoric was administered this medicine to the experiment animals. It was observed that when it were administered to a monkey a substance that facilitates or power to the MAO as is the Reserpina, upon acting the MAO in a way overdone and to destroy with greater intensity the transmitters is reduced the transmission of the nervous stimuli and the animal remains inmóvil,abatido, sad and depressed
This plan illustrates happened what is to the cute to which was administered to him/her/you Reserpina.Al to give to him/her/you Reserpina (R) the molecules of the transmitters (red circles) are destroyed by the MAO and the space sináptico among 2 neurons is I emptied, without transmitting therefore it can not have trasnmisión of nervous impulses.
If to that monkey depressed by the action of the Reserpina we give to him/her/you an opposite medicine that is to say an inhibitor or antagonist of the MAO as is the Iproniazida to be stopped the destructive action of the MAO on the transmitters, abound estos in the space sináptico being facilitated the transmission of the nervous impulses and the animal is recovered of their/its/your/his depression and beginning to run by the cage.
This plan illustrates happened what is upon giving to him/her/you iproniazida to the cute depressed. In spite of the fact that todavia remain remains of reserpina (R) to administers to him/her/you iproniazida is stopped the action of the MAO being stopped the destruction of the transmitters (red circles) that happen to the space sináptico being facilitated the transmission of the nervous stimuli being cured thus the depression that been habia induced to the animal with the first dose of reserpina.
The inhibitors of the MAO were the first antidepressants that they were used in the treatment of the depression but by their/its sound effects have been substituted additionally medicines but sure. In 1958 Roland Kuhn discovered a substance llamda IMIPRAMINA that was very effective for the treatment of the sick depressed.
However the Imipramina acts in a way very different from the Iproniazida. Normally when the transmitter (serotonina,noradre ...etc) is released in the space sináptico (red triangles) is joined or coupled to the receivers of the neighboring neuron to favor the transmission of the nervous stimuli. The remaining transmitter molecules that is to say those which are not joined to the receiving is inactivan through a system of recaptación (arrows) .Es to say the excess of trasmisores present in the space sináptico is reabsorvido or pumped of new toward their/its/your/his origin point (the neuron presináptica) to be destroyed by the MAO.LA IMIPRAMINA (circulos green in the second plan) avtua as a barrier that is opposed or prevented that recaptación or that transmitters pumping toward their/its/your/his origin point and consequently increases the transmitters presence (red triangles) in the space sináptico being favored the trasnmisión of the nervous stimuli and being improved thus the dismal symptoms.
The rich neurons in NORADRENALINA (in green) are concentrated in a kernel called LOCUS COERULEUS. From this kernel the long prolongations (axones) of these neurons establish connections (sinapsis) with the structures of the SYSTEM LÍMBICO (hipocampo,hipotál caudado,amígdala cerebral,corteza frontal ...etc) .Recuérdese that as previously we indicate the system límbico gives ' emotional color to the perceptions and thinks elaborated in our cerebro.Este system modula,regula and controls our emociones,sentimie sexual,bioritmos,m ..etc. On the other hand the rich neurons in SEROTONINA (in blue) are concentrated in some kernels called NÚCLEOS OF THE RAFE. From these kernels the axones of the neurons establish connections also with the SYSTEM LÍMBICO.
