Case history: the discovery of fluoxetine hydrochloride (Prozac).
In the early 1970s, evidence of the role of serotonin (5-hydroxytryptamine or 5-HT) in depression began to emerge and the hypothesis that enhancing 5-HT neurotransmission would be a viable mechanism to mediate antidepressant response was put forward. On the basis of this hypothesis, efforts to develop agents that inhibit the uptake of 5-HT from the synaptic cleft were initiated. These studies led to the discovery and development of the selective serotonin-reuptake inhibitor fluoxetine hydrochloride (Prozac; Eli Lilly), which was approved for the treatment of depression by the US FDA in 1987. Here, we summarize this research and discuss the many challenges that we encountered during the development of fluoxetine hydrochloride, which has now been widely acknowledged as a breakthrough drug for depression.
Wong
David T
DT
Department of Psychiatry, Indiana University School of Medicine, Indianapolis 46202, USA. dtwongindy@iquest.net
Perry
Kenneth W
KW
Bymaster
Frank P
FP
D003863:Depression / Q000188:drug therapy; D017277:Drug Approval / Q000379:methods; D015195:Drug Design; D004345:Drug Industry / Q000266:history / Q000379:methods; D005473:Fluoxetine / Q000266:history* / Q000627:therapeutic use; D049673:History, 20th Century; D006801:Humans
D005473:Fluoxetine