A Case History on the Challenges of Central Nervous System and Dual Pharmacology Drug Discovery - Accounts in Drug Discovery Case Studies in Medicinal Chemistry - page 267

CHAPTER 12
A Case History on the
Challenges of Central Nervous
System and Dual Pharmacology
Drug Discovery
PAUL V. FISH, ANTHONY HARRISON,
FLORIAN WAKENHUT AND GAVIN A. WHITLOCK*
Pfizer Global Research and Development, Ramsgate Road, Sandwich,
Kent CT13 9NJ, UK
12.1 Introduction
Dual serotonin (5-HT) and noradrenaline (NA) reuptake inhibitors (SNRI)
have proven to be an effective treatment for a number of indications, including
depression, anxiety disorders, fibromyalgia, painful peripheral neuropathy and
stress urinary incontinence. 1-5 The search for potent and selective SNRIs has
identified venlafaxine 1, desvenlafaxine 2, milnacipran 3 and duloxetine 4
(Figure 12.1), which are all marketed drugs. 6-10 Furthermore, several small-
molecule SNRIs have been reported to be in early clinical development or
undergoing preclinical optimization and evaluation. 11-14 Hence, the discovery
of new SNRIs with enhanced properties continues to be an attractive target for
the pharmaceutical industry.