Phosphodiesterase inhibitors for cognitive enhancement

Gregory M. Rose, Allen Hopper, Michael De Vivo, Ashok Tehim

Research output: Contribution to journalReview articlepeer-review

116 Scopus citations

Abstract

An effective treatment for age-related cognitive deficits remains an unmet medical need. Currently available drugs for the symptomatic treatment of Alzheimer's disease or other dementias have limited efficacy. This may be due to their action at only one of the many neurotransmitter systems involved in the complex mechanisms that underlie cognition. An alternative approach would be to target second messenger systems that are utilized by multiple neurotransmitters. Cyclic adenosine monophosphate (cAMP) is a second messenger that plays a key role in biochemical processes that regulate the cognitive process of memory consolidation. Prolongation of cAMP signals can be accomplished by inhibiting phosphodiesterases (PDEs). Eleven PDE families, comprised of more than 50 distinct members, are currently known. This review summarizes the evidence demonstrating that rolipram, a selective inhibitor of cAMP-selective PDE4 enzymes, has positive effects on learning and memory in animal models. These data provide support for the general approach of second messenger modulation as a potential therapy for cognitive dysfunction, and specifically suggest that PDE4 inhibitors may have utility for improving the symptoms of cognitive decline associated with neurodegenerative and psychiatric diseases.

Original languageEnglish
Pages (from-to)3329-3334
Number of pages6
JournalCurrent Pharmaceutical Design
Volume11
Issue number26
DOIs
StatePublished - 2005
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Cognition
  • Memory
  • PDE4
  • Rolipram

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