Intracellular cyclic nucleotide levels can be controlled through regulation of either synthesis via respective cyclases or degradation via the phosphodiesterases (PDEs)[3]. Dipyridamole inhibits the phosphodiesterase enzyme that degrades cyclic AMP to 5’-AMP, resulting in the intraplatelet accumulation of cyclic AMP[4]. Inhibition of the erythrocytic nucleoside transport system by dipyridamole (10 μM) evokes the antiaggregatory action of adenosine in whole blood (IC50 congruent to 2 μM)[5]. In an in situ perfused rabbit lung model in which the pulmonary vascular resistance (PVR) was elevated, 0.06 μM dipyridamole reduced elevated PVR by 8.2 +/- 2.8%, and the EC50 for dipyridamole was approximately 0.2 μM[6]. In newborn lambs with persistent pulmonary hypertension of the newborn (PPHN), dipyridamole infused at 0.02 mg/kg/min for 45 min alone significantly decreased pulmonary and systemic blood pressure, decreased pulmonary vascular resistance, and increased pulmonary blood flow[7]. Some potent dipyridamole derivatives are able to increase the primary immune response in mice immunized with sheep red blood cells (SRBC). 10 mg/kg/day of the most potent substance administered in the drinking water increased the number of plaque forming cells (PFC) in spleens of these mice by a factor of about 2 when the treatment was started after immunization[8].
Dipyridamole/双嘧达莫 细胞实验
Cell Line
Concentration
Treated Time
Description
References
BEAS-2B cells
10 μM
8 hours
Validate the anti-ferroptotic effect of Dipyridamole in bronchial epithelial cells
Theranostics. 2024 Oct 21;14(18):6947-6968.
HUVEC cells
5 μM
8 hours
Validate the anti-ferroptotic effect of Dipyridamole in pulmonary endothelial cells
Theranostics. 2024 Oct 21;14(18):6947-6968.
A549 cells
10 μM
8 hours
Screening FDA-approved drug library to identify Dipyridamole as an effective ferroptosis inhibitor
Theranostics. 2024 Oct 21;14(18):6947-6968.
Neutrophils
10 µM
3 hours
Dipyridamole suppresses APS IgG-mediated NETosis via activation of the adenosine A2A receptor
Nat Commun. 2019 Apr 23;10(1):1916.
Dipyridamole/双嘧达莫 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Rats
Bilateral cavernous nerve crush (BCNC) model
Oral
40 mg/kg
Once daily for 4 weeks
To evaluate the therapeutic effects of Dipyridamole on BCNC model rats, it was found that 40 mg/kg Dipyridamole significantly increased penile adenosine levels, improved erectile function, and down-regulated the expression of HIF-1α and TGF-β.
Adv Sci (Weinh). 2024 Aug;11(30):e2306514.
C57BL/6J mice
LPS-induced acute lung injury model
Intraperitoneal injection
10 mg/kg
Pretreatment 1 hour before, lasting for 24 hours
Validate the in vivo anti-ferroptotic and therapeutic effects of Dipyridamole in alleviating lung injury
Theranostics. 2024 Oct 21;14(18):6947-6968.
Athymic male mice
Du145 subcutaneous tumor model
Intraperitoneal injection
40 mg/kg/injection
14 consecutive days, once daily
To evaluate the antitumor efficacy of G47Δ enhanced by DP and DL
Cancer Res. 2010 May 15;70(10):3890-5
Mice
Venous thrombosis model
Intraperitoneal injection
5 mg/kg
Started one day before surgery and continued through the experiment
Dipyridamole mitigates venous thrombosis by suppressing NETosis
Nat Commun. 2019 Apr 23;10(1):1916.
Mice
Partial liver ischemia model
Intravenous injection
0.5mg/25g mouse IV
Single dose, 15 minutes prior
Mice pretreated with dipyridamole showed elevated hepatic adenosine levels, reduced plasma AST and ALT levels, and attenuated hepatic tissue injury after liver ischemia and reperfusion.
Hepatology. 2013 Nov;58(5):1766-78
C57BL/6J mice
Chronic hindlimb ischemia model
Oral
200 mg/kg
Twice daily, starting 3 days prior to ischemia induction and continued throughout the study
Dipyridamole significantly enhances ischemia-induced arteriogenesis through a PKA-dependent eNOS pathway, rapidly restoring ischemic hindlimb blood flow, increasing vascular density and cell proliferation.
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