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K-134, a phosphodiesterase 3 inhibitor, improves gait disturbance and hindlimb blood flow impairment in rat peripheral artery disease models.
MedLine Citation:
PMID:  22659587     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
K-134, a phosphodiesterase 3 (PDE3) inhibitor with anti-thrombotic and anti-hyperplastic activity, is being developed for the treatment of intermittent claudication. We assessed the efficacy of K-134 against gait disturbance in two rat experimental peripheral arterial disease (PAD) models: the bilateral laurate-induced PAD model and femoral artery ligation model. In the laurate-induced peripheral arterial disease model, 1 week of repeated oral administration of K-134 significantly improved gait disturbance. Cilostazol and clopidogrel did not significantly improve gait disturbance. Repeated oral administration of K-134 and cilostazol significantly improved gait disturbance in the femoral artery ligation model. We evaluated the effects of K-134 and cilostazol treatment on hindlimb blood flow pre- and post-treadmill exercise in this model by laser Doppler perfusion imaging. Both drugs increased hindlimb blood flow both pre- and post-treadmill exercise after 1 week of treatment. After 4 weeks of drug treatment, without preceding drug administration which is supposed to exert acute effects on vessel walls, both drugs significantly increased hindlimb blood flow after exercise. Moreover, K-134 at 30mg/kg significantly prolonged walking distance. These results suggest that K-134 may be useful for treating intermittent claudication.
Authors:
Yusuke Sasaki; Hideo Suzuki; Shinsuke Itoh; Hideo Yoshida; Shoichi Kondo; Keisuke Inoue; Sohei Tanabe
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-30
Journal Detail:
Title:  European journal of pharmacology     Volume:  -     ISSN:  1879-0712     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-6-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier B.V.
Affiliation:
Tokyo New Drug Research Laboratories, Kowa Company, Ltd., 2-17-43, Noguchi-cho, Higashimurayama, Tokyo 189-0022, Japan.
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