ArticleDaru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences2015
Metabolic effects of newly synthesized phosphodiesterase-3 inhibitor 6-[4-(4-methylpiperidin-1-yl)-4-oxobutoxy]-4-methylquinolin-2(1H)-one on rat adipocytes.
Article in Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed, 6 citations in OpenAlex.
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4 authors at 1 institution in 1 country.
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Abstract
backgroundClinical use of selective PDE3 inhibitors as cardiotonic agents is limited because of their chronotropic and lipolytic side effects. In our previous work, we synthesized a new PDE3 inhibitor named MC2 (6-[4-(4-methylpiperidin-1-yl)-4-oxobutoxy]-4-methylquinolin-2(1H)-one) which produced a high positive inotropic action with a negative chronotropic effect. This work was done to evaluate the effects of MC2 on adipocytes and compare its effects with those of amrinone and cilostamide.
methodsPreadipocytes were isolated from rat adipose tissue and differentiated to adipocyte in the presence of cilostamide, amrinone or MC2. Lipolysis and adipogenesis was evaluated by measuring glycerol level and Oil Red O staining, respectively. Adipocyte proliferation and apoptosis were determined with MTT assay and Annexin V/PI staining, respectively.
resultsDifferentiation to adipocyte was induced by amrinone but not by cilostamide or MC2. Basal and isoproterenol-stimulated lipolysis significantly increased by cilostamide (p<0.05). Similarly, amrinone enhanced the stimulated lipolysis (p<0.01). On the other hand, MC2 significantly decreased both adipogenesis (p<0.05) and stimulated lipolysis (p<0.001). Also, incubation of differentiated adipocytes with MC2 caused the loss of cell viability, which was associated with the elevation in apoptotic rate (p<0.05).
conclusionOur data indicate that selective PDE3 inhibitors produce differential effects on adipogenesis and lipolysis. MC2 has proapoptotic and antilipolytic effects on adipocytes and does not stimulate adipogenesis. Therefore, in comparison with the clinically available selective PDE3 inhibitors, MC2 has lowest metabolic side effects and might be a good candidate for treatment of congestive heart failure.
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