Page "Sertraline" Paragraph 46

The history of sertraline dates back to the early 1970s, when Pfizer chemist Reinhard Sarges invented a novel series of psychoactive compounds based on the structures of neuroleptics chlorprothixene and thiothixene.

Further work on these compounds led to tametraline, a norepinephrine and weaker dopamine reuptake inhibitor.

Development of tametraline was soon stopped because of undesired stimulant effects observed in animals.

A few years later, in 1977, pharmacologist Kenneth Koe, after comparing the structural features of a variety of reuptake inhibitors, became interested in the tametraline series.

He asked another Pfizer chemist, Willard Welch, to synthesize some previously unexplored tametraline derivatives.

Welch generated a number of potent norepinephrine and triple reuptake inhibitors, but to the surprise of the scientists, one representative of the generally inactive cis-analogs was a serotonin reuptake inhibitor.

Welch then prepared stereoisomers of this compound, which were tested in vivo by animal behavioral scientist Albert Weissman.

The most potent and selective (+)- isomer was taken into further development and eventually named sertraline.

Weissman and Koe recalled that the group did not set up to produce an antidepressant of the SSRI type — in that sense their inquiry was not " very goal driven ", and the discovery of the sertraline molecule was serendipitous.

According to Welch, they worked outside the mainstream at Pfizer, and even " did not have a formal project team ".

The group had to overcome initial bureaucratic reluctance to pursue sertraline development, as Pfizer was considering licensing an antidepressant candidate from another company.