| Title | Antiatherosclerotic properties of the novel squalene synthase inhibitor EP2306 in vivo | |
| Authors | Anna Tavridou¹, Loukas Kaklamanis², Apostolos Papalois³, Aggeliki P. Kourounakis⁴, Panos N. Kourounakis⁵, Avghi Charalambous³ and Vangelis G. Manolopoulos¹
1. Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece 2. Onassis Cardiac Surgery Center, Department of Pathology, Athens, Greece 3. ELPEN Pharmaceutical Co Inc., 95 Marathonos Av., Pikermi, Greece 4. Department of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, Athens, Greece 5. Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, Thessaloniki, Greece |
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| Citation | Tavridou, A., Kaklamanis, L., Papalois, A., Kourounakis, A.P., Kourounakis, P.N. et al: Antiatherosclerotic properties of the novel squalene synthase inhibitor EP2306 in vivo blood, Epitheorese Klin. Farmakol. Farmakokinet. 20(2): 111-113 (2006) | |
| Publication Date | Accepted for publication: 19-20 May 2006 | |
| Full Text Language | English | |
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| Keywords | Squalene synthase inhibitor, 2-biphenylmorpholine compounds, hypercholesterolemia, atherosclerosis, rabbit. | |
| Other Terms | review article | |
| Summary | We have recently shown that EP2306, a novel 2-biphenylmorpholine derivative, is a potent inhibitor of squalene synthase and possesses antioxidant properties in vitro and in vivo. In the present study, we investigated the antiatherosclerotic effect of this compound in the cholesterol-fed rabbit. After one month of treatment, EP2306 significantly inhibited atherosclerotic plaque formation dose-dependently in the ascending and the descending aorta of treated animals. The most effective dose, 2 mg/kg, inhibited atherosclerosis by approximately 70 % as compared to placebo animals. In contrast to the effect on atherosclerosis, EP2306 had only a low and not significant effect on total and LDL-cholesterol in comparison with placebo animals. No macroscopic or microscopic signs of toxicity could be found in any major organ of hypercholesterolemic rabbits in this study. EP2306 attacks the atherosclerotic plaque formation chain on several different fronts and it might prove to be useful for treatment of atherosclerosis in humans. However, extended pharmacodynamic and toxicological studies will be required to determine whether EP2306 can be used in conjunction with current therapies for better results in the treatment of hyperlipidemia-related diseases in humans. | |
| References | 1. MacFarlane P.W., McKillop J.H., Packard C.J.: Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N. Engl. J. Med. 333: 1301-1307 (1995)
2. Group S.: Randomised trial of cholesterol lowering in 4444 patients with coronary heartdisease: the Scandinavian Simvastatin Survival Study (4S). Lancet 344: 1383-1389 (1994) 3. Chrysselis M.C., Rekka E.A., Kourounakis P.N.: Hypocholesterolemic and hypolipidemic activity of some novel morpholine derivatives with antioxidant activity. J. Med. Chem. 43: 609-612 (2000) 4. Chrysselis M.C., Rekka E.A., Siskou I.C., Kourounakis P.N.: Nitric oxide releasing morpholine derivatives as hypolipidemic and antioxidant agents. J. Med. Chem. 45: 5406-5409 (2002) 5. Tavridou A., Manolopoulos V.G.: Antioxidant properties of two novel 2-biphenylmorpholine compounds (EP2306 and EP2302) in vitro and in vivo. Eur. J. Pharmacol. 505: 213-221 (2004): 6. Tavridou A., Kaklamanis L., Megaritis G., Kourounakis A.P., Papalois A., Roukounas D., Rekka E.A., Kourounakis P.N., Charalambous A., Manolopoulos V.G.: Pharmacological char- acterization in vitro of EP2306 and EP2302, potent inhibitors of squalene synthase and lipid biosynthesis. Eur. J. Pharmacol., in press, 2006 |
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| Relative Papers |
Online ISSN 1011-6575
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Articles published in this Journal are Indexed or Abstracted in: • Chemical Abstracts • Elsevier’s Bibliographic Databases: Scopus, EMBASE, EMBiology, Elsevier BIOBASE SCImago Journal and Country Rank Factor
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