Role of serendipity in the discovery of classical antidepressant drugs:Applying operational criteria and patterns of discovery  

作　　者：Francisco López-Muñoz Pilar D’Ocón Alejandro Romero JoséA Guerra CecilioÁlamo 

机构地区：[1]Faculty of Health,University Camilo JoséCela,Villanueva de la Cañada 28692,Madrid,Spain [2]“Hospital 12 de Octubre”Research Institute(i+12),Avda.de Córdoba,s/n,Madrid 28041,Spain [3]Department of Pharmacology,Faculty of Pharmacy,University of Valencia,Avda.Vicent Andres Estelles,s/n,Valencia 46100,Spain [4]Department of Pharmacology and Toxicology,Faculty of Veterinary Medicine,Complutense University,Avda.Puerta de Hierro,s/n,Madrid 28040,Spain [5]Department of Pharmacology and Toxicology,Faculty of Pharmacy,Complutense University,Pl.de Ramón y Cajal,s/n,Madrid 28040,Spain [6]Department of Biomedical Sciences(Pharmacology Area),Faculty of Medicine and Health Sciences,University of Alcalá,Campus Científico-Tecnológico,Crta.de Madrid-Barcelona,Alcaláde Henares 28871,Madrid,Spain

出　　处：《World Journal of Psychiatry》2022年第4期588-602,共15页世界精神病学杂志

摘　　要：The role played by serendipity in the origin of modern psychopharmacology has proven to be controversial in scientific literature.In its original meaning(Walpole),serendipity refers to discoveries made through a combination of accidents and sagacity.We have implemented an operational definition of serendipity based on finding something unexpected or unintended,regardless of the systematic process that led to the accidental observation,and we have established four different patterns of serendipitous attributability.In this paper,we have analyzed the role of serendipity in the discovery and development of classical antidepressant drugs,tricyclic antidepressants and monoamine oxidase inhibitors as well as heterocyclic,“atypical”or“second generation”antidepressants.The discovery of the antidepressant properties of imipramine and iproniazid,the prototypes of tricyclic antidepressants and monoamine oxidase inhibitors,respectively,fits the mixed type II pattern;initial serendipitous discoveries(imipramine was an antipsychotic and iproniazid was an antituberculosis agent)led secondarily to non-serendipitous discoveries.But the other components of these two families of drugs were developed specifically as antidepressants,modifying the chemical structure of the series leaders,thereby allowing all of them to be included in the type IV pattern,characterized by the complete absence of serendipity.Among the heterocyclic drugs,mianserin(originally developed as an antihistamine)also falls into the type II pattern.

关 键 词：Serendipity Antidepressants IMIPRAMINE Iproniazid PSYCHOPHARMACOLOGY History of neurosciences 

分 类 号：O62[理学—有机化学]