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Phosphodiesterases as targets for intermittent claudication
Yongge Liu1, Yasmin Shakur, Junichi Kambayashi
1Otsuka Maryland Medicinal Laboratories, Rockville, MD, USA. yonggel@yahoo.com
Handbook of Experimental Pharmacology
|June 23, 2011
Summary
Intermittent claudication (IC) symptoms, caused by peripheral arterial disease (PAD), can be improved with cilostazol. This phosphodiesterase 3 (PDE3) inhibitor offers multifactorial benefits for patients with leg pain during exercise.
Area of Science:
- Vascular Medicine
- Pharmacology
- Biochemistry
Background:
- Intermittent claudication (IC) is a common manifestation of lower extremity peripheral arterial disease (PAD), primarily caused by atherosclerosis.
- IC symptoms include exercise-induced leg muscle pain and fatigue due to an oxygen supply-demand mismatch.
- Current pharmacological options for IC are limited, with cilostazol and pentoxifylline being the only indicated drugs.
Purpose of the Study:
- To review the pharmacological actions of cilostazol in treating intermittent claudication.
- To discuss the rationale and challenges of targeting phosphodiesterases (PDEs) for IC treatment.
- To explore strategies for developing novel and more effective therapies for IC.
Main Methods:
- Literature review of studies on intermittent claudication, peripheral arterial disease, and phosphodiesterase inhibitors.
- Analysis of cilostazol's mechanism of action and clinical efficacy.
- Discussion of current therapeutic limitations and future research directions.
Main Results:
- Cilostazol, a PDE3 inhibitor, significantly improves walking distance and quality of life in IC patients.
- Cilostazol exerts multifactorial effects, including antiplatelet, endothelial, smooth muscle, and lipid-modulating actions.
- Existing treatments for IC have limitations, highlighting the need for improved therapeutic strategies.
Conclusions:
- Cilostazol represents a valuable therapeutic option for managing intermittent claudication symptoms.
- Targeting PDEs offers potential for developing new treatments, but challenges remain.
- Further research is needed to optimize PDE-targeted therapies for peripheral arterial disease.
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