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FEATURES OF THE PHARMACOLOGICAL ACTION AND USE OF
DIPYRIDAMOLE IN THE PREVENTION AND TREATMENT OF VIRAL
INFECTIONS
Ibragimova Nargiza Mirzazhanovna
Abstract:
The review presents current information on the molecular mechanisms of antiplatelet,
vasodilatory, angioprotective, antifibrotic and immunomodulatory effects of dipyridamole. The
paper presents data from domestic studies devoted to testing the efficacy and safety of
dipyridamole (Curantil) in the prevention of acute respiratory viral infections and the treatment
of recurrent stress-induced opportunistic infectious diseases, which show that dipyridamole is an
effective combination drug with a good safety profile and the ability to exert a positive effect on
blood vessels in metabolic disorders in patients with a complicated medical history, and allows
for effective prevention of acute respiratory viral infections in high-risk patients.
Kеywоrds:
dipyridamole, molecular mechanisms of action, prevention and treatment of acute
respiratory viral infections, organoprotective action.
INTRОDUСTIОN
The most common infectious disease is acute respiratory viral infection (ARVI). The number of
complications with ARVI, especially with influenza, reaches 20-30% during epidemics. The
main causes of complications are dysfunction of the div's immune system with a decrease in
antibacterial resistance and the addition of a bacterial infection in high-risk patients. Etiotropic
antiviral therapy exists only for the treatment of influenza: neuraminidase inhibitors (oseltamivir),
M2 protein blockers (adamantanes) and a fusion inhibitor (umifenovir). For other types of ARVI,
drugs of pathogenetic and symptomatic types of action are used [1].
MАTЕRIАLS АND MЕTHОDS
The best way to combat complications of ARVI is to prevent the disease itself. The development
of infection can be prevented by targeted activation of one of the most ancient mechanisms of the
div's defense - the interferon system (IFN). IFN is a family of local regulation proteins that can
activate intracellular processes and intercellular interactions that ensure the div's resistance to
viral infections, enhance the innate and acquired immune response, and modulate the processes
of development and death of unchanged and tumor cells. The div's resistance to viral infections
and a number of other diseases largely depends on the activity of IFN genes. The effects of IFN
are indirect – activation of IFN specific receptors causes a cascade of cellular processes leading
to the induction of genes encoding the synthesis of many proteins that provide the antiviral
effects, antitumor and antiproliferative action of IFN. Proteins induced by IFN include: enzymes,
receptors, transporters, cytokines, chemokines and other factors. The production of IFN by cells
is transient, temporary – normally “silent” IFN genes are induced under the influence of products
of viral and microbial origin and chemical inductors (high- and low-molecular) [2].
RЕSULTS АND DISСUSSIОN
For the prevention of ARVI, IFN preparations, IFN inducers and other immunomodulators are
often used. Popular IFN preparations have a number of drawbacks from a pharmacological point
of view, the most important of which is the problem of bioavailability (this does not apply to
injectable IFN, but this method of administration is not used for the prevention of ARVI). A
fairly large peptide molecule of IFN will be destroyed and lose its properties when taken orally,
and when applied locally, it will not be able to overcome tissue barriers. Nevertheless, local use
of IFN has a right to exist, since in the mucous membrane they stimulate local immunity, thereby
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volume 4, issue 3, 2025
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strengthening the protection of potential infection gates. A more popular class of drugs for the
prevention of viral infections are low-molecular IFN inducers, which can be taken orally. The
problem of drug prevention and treatment of ARVI is that high-risk patients, i.e. For those who
especially need medications, medications included in the treatment standards are often
contraindicated. In particular, pregnant women, overweight patients and patients with diabetes,
older patients, and children are at risk of severe and complicated influenza. Therefore, among
IFN inducers, a special place is occupied by dipyridamole, a well-studied drug with a favorable
safety profile, which is widely used in clinical practice as an antiplatelet agent, vasodilator, and
IFN inducer. To exhibit IFN-inducing activity, dipyridamole must be administered in
significantly smaller doses (4–8 times smaller than generally accepted therapeutic doses)
according to a special regimen adopted for most low-molecular IFN inducers (once a week) [3].
The antiplatelet effect is associated with several events. Firstly, dipyridamole causes an increase
in the concentration of adenosine in tissue by inhibiting the reuptake of adenosine by cells
(nucleoside transporter ENT1) and blocking its catabolism – adenosine desamenase (P. Gresele,
1986; P. Ferrandon, 1994; C. Wang, 2013). Adenosine exhibits the properties of a platelet
inhibitor (stimulates adenylate cyclase – AC through A2A receptors). Secondly, in human
platelets, dipyridamole enhances the nitric oxide – NO/cyclic guanosine monophosphate – cGMP
signal and its consequences, such as phosphorylation of serine 239 VASP, inhibition of
thromboxane synthase and serotonin secretion (B. Aktas, 2003). Thirdly, there is inhibition of
the intracellular PDE enzyme – non-selective in high doses and selective – PDE type 5 (cGMP)
and PDE type 8 (cyclic adenosine monophosphate – cAMP) – in therapeutic (V. Ahn, 1989; S.
Francis, 2011), responsible for the breakdown of cyclic nucleotides. The accumulation of cGMP
and cAMP in the cell (platelet) causes a decrease in the concentration of free Ca2+ ions, as a
result of which contractile proteins (microtubules and microfilaments) do not polymerize, which
is absolutely necessary for the transport of receptorosomes to the membrane and the exposure of
IIb/IIIa receptors on the cell surface (actually, platelet activation) [4].
СОNСLUSIОN
Dipyridamole is an effective drug with complex action, its effects include antiplatelet, anti-
ischemic and immunomodulatory action. The drug improves the rheological properties of the
blood, promotes angiogenesis and the development of collaterals, has an angio- and
organoprotective effect (neuro- and nephroprotection). It is used not only for cardiovascular
diseases, but also in obstetrics. Its immunomodulatory effect is successfully used for the
prevention of acute respiratory viral infections, influenza and the treatment of opportunistic
infections.
RЕFЕRЕNСЕS
1. Ahn HS, Crim W, Romano M et al. Effects of selective inhibitors on cyclic nucleotide
phosphodiesterases of rabbit aorta. Biochem Pharmacol 2019; 38:3331–9.
2. Aktas B, Utz A, Hoenig-Liedl P et al. Dipyridamole enhances NO/cGMP-mediated
vasodilator-stimulated phosphoprotein phosphorylation and signaling in human platelets: in vitro
and in vivo/ex vivo studies. Stroke 2013; 34(3):764–9.
3. Balakumar P, Nyoa YH, Renushiaa R et al. Classical and pleiotropic actions of dipyri-damole:
Not light enough to illuminate the dark tunnel? Pharmacol Res 2014; 87: 144–50. DOI:
10.1016/j.phrs.2014.05.008.
4. Balakumar P, Varatharajan R, Nyo YH et al. Fenofibrate and dipyridamole treatments in low-
doses either alone or in combination blunted the development of nephropathy in diabetic rats.
Pharmacol Res 2014; 90: 36–47. DOI: 10.1016/j.phrs.2014.08.008.
