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Investigational phosphodiesterase inhibitors in phase I and phase II clinical trials for Alzheimer's disease
- Source :
- Expert Opinion on Investigational Drugs, 26(9), 1033-1048. Routledge/Taylor & Francis Group
- Publication Year :
- 2017
-
Abstract
- INTRODUCTION: Phosphodiesterase (PDE) inhibitors improve signaling pathways in brain circuits by increasing intracellular cyclic adenosine monophosphate (cAMP) and/or cyclic guanosine monophosphate (cGMP). In the last decade, the first clinical studies investigating selective PDE inhibitors in Alzheimer's disease (AD) have been initiated, based on their positive effects on cognitive processes and neuroprotection in numerous animal studies. Areas covered: This article reviews the clinical studies investigating the pro-cognitive/neuroprotective effects of PDE inhibitors in patients with AD, as well as in age-associated memory impaired elderly and patients with mild cognitive impairment (MCI), the prodromal stage of AD. PDE inhibitors will also be discussed with respect to adverse effects including safety and tolerability. Expert opinion: The limited available data of clinical studies with PDE inhibitors tested in different populations of AD patients do not allow the drawing of any concrete conclusion yet. Currently, studies with a PDE3 (cilostazol) or PDE9 inhibitor (BI 409,306) are still ongoing in patients with MCI or AD, respectively. Studies with PDE4 inhibitors (HT-0712, roflumilast and BPN14770) in healthy elderly and elderly with age-associated memory impairments indicate that the optimum dose and/or inhibiting the most relevant PDE isoform hold great promise when tested in the appropriate population of patients with MCI or AD eventually.
- Subjects :
- 0301 basic medicine
cognition
ENHANCES MEMORY
IMPROVES MEMORY
Phosphodiesterase Inhibitors
Phases of clinical research
Disease
10A INHIBITORS
Pharmacology
chemistry.chemical_compound
DOUBLE-BLIND
0302 clinical medicine
SYNAPTIC PLASTICITY
Cyclic AMP
Medicine
Pharmacology (medical)
Cyclic GMP
PDE4D INHIBITORS
Clinical Trials, Phase I as Topic
Phosphodiesterase
General Medicine
MOUSE MODEL
Alzheimer's disease
LONG-TERM-MEMORY
neuroprotection
Signal transduction
phosphodiesterase
Signal Transduction
Neuroprotection
COGNITIVE PERFORMANCE
03 medical and health sciences
Clinical Trials, Phase II as Topic
mild cognitive impairment
Alzheimer Disease
cAMP
Journal Article
Animals
Humans
Cognitive Dysfunction
Cyclic adenosine monophosphate
Adverse effect
Cyclic guanosine monophosphate
Aged
business.industry
Drugs, Investigational
cGMP
030104 developmental biology
chemistry
Drug Design
CEREBRAL-BLOOD-FLOW
business
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 13543784
- Database :
- OpenAIRE
- Journal :
- Expert Opinion on Investigational Drugs, 26(9), 1033-1048. Routledge/Taylor & Francis Group
- Accession number :
- edsair.doi.dedup.....eb220b2297c2e86874c59f78cb0c9fb8