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Interesse Terapêutico dos Inibidores da Monoamina Oxidase
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Orientador(es)
Resumo(s)
A família das monoamina oxidases (MAO) teve a sua descoberta há várias décadas. A posterior descoberta dos diversos substratos na qual actua, bem como a sua presença elevada em diversos tecidos do organismo, revelou a sua importância biológica, aumentando, consequentemente, o interesse nesta como potencial alvo terapêutico.
Através da distinção entre os dois subtipos de MAO, MAO A e MAO B, com divergências nas moléculas que metabolizam e no seus locais de maior concentração, encontrou-se ainda uma potencial forma de modelar a selectividade dos seus possíveis efeitos terapêuticos.
Os inibidores da monoamina oxidase (iMAO) não tiveram um percurso fácil até serem considerados como alternativas terapêuticas. Apesar dos seus claros benefícios, a conhecida “cheese reaction”, uma reacção adversa grave e muitas vezes fatal, acabou por impedir que estes se tornassem opções de primeira linha no tratamento da depressão, o seu primeiro efeito terapêutico descrito.
Com a descoberta de novos iMAO capazes de evitar a “cheese reaction”, o interesse terapêutico sobre esta classe de moléculas ressurgiu. Nesta monografia pretende-se mostrar o percurso histórico dos iMAO, bem como caracterizar o seu interesse terapêutico actual e o seu potencial futuro.
The monoamine oxidase (MAO) family was discovered several decades ago. Later, the discovery of the different substrates that it metabolizes, along with its high presence in numerous human tissues, showed its biological significance, increasing its interest as a potential therapeutic target. Through the distinction of the two MAO subtypes, MAO A and MAO B, differing in the molecules they metabolize and in the biological tissues where they have higher concentrations, a potential pathway to increase their therapeutic selectivity was found. The monoamine oxidase inhibitors (MAOi) didn’t have a easy path in becoming valid therapeutic alternatives. In spite of their clear benefits, the well known “cheese reaction”, a serious and potentially fatal adverse reaction, kept them from becoming first line choices in the treatment of depression, their first described therapeutic effect. With the discovery of new MAOi capable of avoiding the “cheese reaction”, the therapeutic interest in this class was renewed. This thesis intends to show the historic pathway of MAOi, as well as their current therapeutic interest and their future potential.
The monoamine oxidase (MAO) family was discovered several decades ago. Later, the discovery of the different substrates that it metabolizes, along with its high presence in numerous human tissues, showed its biological significance, increasing its interest as a potential therapeutic target. Through the distinction of the two MAO subtypes, MAO A and MAO B, differing in the molecules they metabolize and in the biological tissues where they have higher concentrations, a potential pathway to increase their therapeutic selectivity was found. The monoamine oxidase inhibitors (MAOi) didn’t have a easy path in becoming valid therapeutic alternatives. In spite of their clear benefits, the well known “cheese reaction”, a serious and potentially fatal adverse reaction, kept them from becoming first line choices in the treatment of depression, their first described therapeutic effect. With the discovery of new MAOi capable of avoiding the “cheese reaction”, the therapeutic interest in this class was renewed. This thesis intends to show the historic pathway of MAOi, as well as their current therapeutic interest and their future potential.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2013
Palavras-chave
Monoamina oxidase A Monoamina oxidase B Inibidores da monoamina oxidase Depressão Doença de Parkinson Interesse terapêutico Mestrado Integrado - 2013