Drug development serendipity

The history of drug development for schizophrenia reflects the value of serendipity and may point toward future advances. 

Most researchers and drug companies, however, still appear to he conhdent that combinatorial chemistry holds untold promise for the future. Though they often admit that there is little to show hy way of approved products that have evolved from combinatorial techniques, they point out that the early years of new technologies are often marked by similar stories of limited success. Eventually, they say, comhinatorial chemistry will take its place with natural products, trial and error, serendipity, and other traditional roads to drug development as an essential tool in the design and production of new pharmaceutical products. 

Serendipity in drug development Discovery of and development of stable co-crystals... 

The next milestone in the development of organic synthesis was the preparation of the first synthetic dye, mauveine (aniline purple) by Perkin in 1856 Perkin, 1856, 1862). This is generally regarded as the first industrial organic synthesis. It is also a remarkable example of serendipity. Perkin s goal was the synthesis of the antimalarial drug quinine by oxidation of N-allyl toluidine (Fig. 2.4). 

Examples abound regarding the role of serendipity in the discovery of new therapeutic approaches, which on closer examination usually turned out to be the result of clinicians paying attention to unexpected clinical effects rather than discounting them. For example, lithium was tried first for hypertension, chlorpro-mazine was initially developed as an anesthetic, and imipramine was originally regarded as an antihistamine and an antipsychotic agent. Without astute clinical observations, these drugs would not have found their niche, nor would clozapine have been revived for the benefit of millions of the most difficult to treat schizophrenic patients. Other examples include the expanded indications of newer... 

Serendipity has played a major role in the discovery of most classes of psychotropic drugs. For example, the observation that the first antidepressants, the tricyclic antidepressants and the monoamine oxidase inhibitors, impeded the reuptake of biogenic amines into brain slices, or inhibited their metabolism, following their acute administration to rats, provided the experimenter with a mechanism that could be easily investigated in vitro. Such methods led to the development of numerous antidepressants that differed in their potency, and to some extent in their side effects (for example, the selective serotonin reuptake inhibitors) but did little to further the development of novel antidepressants showing greater therapeutic efficacy. The accidental discovery of atypical antidepressants such as mianserin led to the broadening of the basis of the animal models... 

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