Non-Classical Effects of the cAMP Accumulation Activators In Vivo

Abstract

Purpose : Wound-healing dipyridamole- and papaverine-based aerosols (D1/D2) as activators of the accumulation of cyclic adenosine monophosphate are promising drugs that can accelerate wound healing in wound processes of various origins. Methods: 128 rats were used in the study, including 38 in a pharmacological experiment on a model of stencil wounds and 90 in an experiment that studied the effect of spray on the number of CD34 cells in the blood of rats with chemically induced immunodeficiency. Immunodeficiency was caused by the fivefold administration of cyclophosphamide and prednisone. The expression level of CD34 was determined using flow cytofluorimeter. Results: Dipyridamole- and papaverine-based aerosols of two compositions (with and without ascorbic acid) have pronounced reparative properties, significantly accelerating epithelialization and healing of stencil wounds in rats. In terms of this type of action, they are somewhat superior to dexpanthenol. Dipyridamole- and papaverine-based aerosols have the ability to produce beneficial effect on the entire body’s immune system by stimulating the division of pluripotent CD34 cells. The combined effect of papaverine and dipyridamole on tissues leads to selective stimulation of the division of pluripotent cells in the wound, and contributes to a six-fold acceleration of restoration of the animal’s immune system after induced immunodeficiency. Conclusion: Topical application of D1/D2 aerosol samples on the skin of rats contributed to a statistically significant acceleration of regeneration processes. In terms of the appearance of granulations and epithelialization of wounds, D1/D2 aerosols were superior to dexpanthenol ointment.

The effect of papaverine on tendon healing and adhesion in rats following Achilles tendon repair

“…[ 28 ] Another study showcased the ability of topically applied endogenous stem cells to accelerate wound healing significantly in a diabetic rat model. [ 29 ] In a study by Martynov et al,[ 9 ] a 4×1 cm wound was created, and aerosol forms of papaverine and dipyridamole, another phosphodiesterase inhibitor, were investigated for their effects on wound healing at various time points. The results confirmed the superiority of papaverine and dipyridamole over dexpanthenol in terms of epithelialization, indicating their positive effect on wound healing and pluripotent CD34 cell stimulation.…”

“…Papaverine, an opioid analog possessing myorelaxant and vasodilator effects on vascular smooth muscles, finds application in treating ischemia caused by spasms in the heart, brain, and peripheral blood vessels. [ 8 ] While a study reported that the aerosol form of papaverine accelerates wound healing and stimulates pluripotent CD34 cells,[ 9 ] another study demonstrated its application in a cream form on seven skin flaps, resulting in increased flap survival. [ 10 ] However, no prior research has explored the influence of papaverine on tendon healing.…”

Therapeutic Potential of Pentoxifylline in Paraquat-Induced Pulmonary Toxicity: Role of the Phosphodiesterase Enzymes

“…Among intracellular messengers, cAMP and cGMP play pivotal roles in numerous biological processes, including visceral motility, reproduction, immune and inflammatory responses, vascular resistance, and cardiac output [8]. Intracellular levels of these second messengers are intricately regulated by the balance between synthesizing enzymes such as adenylate cyclase and guanylate cyclase and catabolic enzymes like phosphodiesterase enzymes (PDEs) [9].…”