The Discovery of UK-390957: the Challenge of Targeting a Short Half-life, Rapid T SSRI - Accounts in Drug Discovery Case Studies in Medicinal Chemistry - page 142

CHAPTER 7
The Discovery of UK-390957:
the Challenge of Targeting a
Short Half-life, Rapid T max
SSRI
MARK D. ANDREWS AND DONALD S. MIDDLETON
Worldwide Medicinal Chemistry, Pfizer Global Research and Development,
Ramsgate Road, Sandwich, Kent CT13 9NJ, UK
7.1 Introduction: SSRIs and Premature Ejaculation
Since the launch of the first selective serotonin re-uptake inhibitors (SSRIs) in
the 1980s, this class of drugs has become extremely important for the man-
agement of depression and other psychiatric disorders, and indeed has become
one of the most widely prescribed class of drugs in the developed world. 1
Although SSRIs are generally extremely well tolerated they do cause some
sexual side effects, with delayed ejaculation and absent or delayed orgasm being
the most commonly reported. 2-4 While this is clearly a problem for people with
normal sexual function, this can be an advantage for men suffering from pre-
mature ejaculation (PE).
PE is defined in the Statistical Manual of Psychiatry as ''persistent or recur-
rent onset of orgasm and ejaculation with minimal sexual stimulation before,
upon or shortly after penetration and before the person wishes it''. 5 With pre-
valence estimates varying widely from 5 to 40%, 6,7 it is the most common male
sexual disorder across all age groups and is associated with ''marked distress or