ADMET considerations for phosphodiesterase-5 inhibitors

Rezvanfar, Mohammad Amin; Rahimi, Hamid Reza; Abdollahi, Mohammad

doi:10.1517/17425255.2012.698610

Cited by 19 publications

(7 citation statements)

References 111 publications

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“…As a methylxanthine derivative with a nonselective PDE inhibitory function, PTX has a wide scope of medical applications. For example, various surveys have shown multiple beneficial effects of PTX in hyperinflammation [37], suppression of OS [15,16], improvement of various ROS-related tissue injury models in which conventional antioxidants were not very effective [38,39]. It also improves fertility and increases clinical pregnancy rate through its antioxidant trait [1].…”

Section: Discussionmentioning

confidence: 99%

Cellular and molecular mechanisms of pentoxifylline's beneficial effects in experimental polycystic ovary

et al. 2015

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Section: Discussionmentioning

confidence: 99%

Cellular and molecular mechanisms of pentoxifylline's beneficial effects in experimental polycystic ovary

et al. 2015

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“…For all drug developments, pharmacokinetic profiling by ADMET (absorption, distribution, metabolism, excretion, and toxicity) is a significant aspect (Rezvanfar et al, 2012).…”

Section: Critical Aspects Of Drug Delivery and Dosage Form Developmentsmentioning

confidence: 99%

Significance of Ligand-Anchored Polymers for Drug Targeting in the Treatment of Colonic Disorders

2020

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Treatment of a variety of bowel diseases like Crohn's disease, ulcerative colitis, colonic cancers, colonic pathologies, and systemic delivery of drugs at the target sites can be done with the help of targeted drug delivery technique. Conventional colon specific drug delivery systems lack specificity and release significant amount of drug prior reaching the target site. Hence, efficient drug delivery system that ensures effective release of the drug at the colon is still a sought after research arena. Ligand anchored therapy is a strong and effective approach to execute drug delivery in selective target cells, for both, diagnostic, as well as therapeutic reasons. Compared to the regular drugs, such ligand anchored therapy provides added benefit of minimum toxicity and few side effects. Discovery of overexpressed receptors on diseased cells, as compared to healthy cells led to the emergence of active drug targeting. Further, drug resistance constitutes one of the major reasons of the failure of chemotherapy and presents a major obstacle for the effective treatment. The reason behind drug resistance is exposure of pathological cells/pathogens to sub-therapeutic levels of drugs due lack of specificity of therapeutics. Active targeting, specifically taken up by the target cells, can warrant exposure of pathological cells/ pathogens to high drug load at the target and sparing non-target cells hence minimal damage to normal cells and least chance of drug resistance. Many ligands like antibodies, aptamers, peptides, folate, and transferrin have been discovered in the past few years. The design of nanocarriers can be incorporated with many different functions which enables functions like imaging and triggered intracellular drug release. The present review article focuses on advances in ligand anchored therapy and its significance on the progress of targeted nanocarriers. It will also establish novel concepts like multitargeting and multi-functional nanocarriers for the treatment of colonic disorders.

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“…Furthermore, TAD is more selective than other PDE5Is, which cross-react with PDE6 [10]. Thus, TAD is expected to have fewer side effects [11]. TAD crosses the blood-brain barrier after oral administration and achieves high enough concentration to inhibit PDE5 in the brain to produce more cognitive benefit than sildenafil [12].…”

Section: Introductionmentioning

confidence: 99%

Improvement of cognitive dysfunction by a novel phosphodiesterase type 5 inhibitor, Tadalafil

Otari¹,

Patil²,

Upasani³

2022

Fundamemntal Clinical Pharma

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There is substantial evidence for the modulatory role of cyclic guanosine monophosphate (cGMP)‐specific phosphodiesterases (PDEs) in memory and synaptic plasticity, and an increase in intracellular cGMP facilitates these processes. The present study was aimed at the neuropharmacological investigations of tadalafil (TAD 5, 10, and 20 mg/kg, p.o.) and further involvement of nitric oxide (NO)‐cGMP in its effects. The effects of tadalafil and its combination with NG‐nitro‐L‐arginine methyl ester (L‐NAME) were investigated in scopolamine‐ and diabetes‐induced cognitive dysfunction using elevated plus maze (EPM) and object recognition (ORT) tests. The results of EPM revealed that the scopolamine‐ and diabetes‐induced learning and memory deficit was dose dependently attenuated after administration of TAD (TAD 10 and 20 mg/kg, p.o.) in both paradigms studied. Administration of L‐NAME (20 mg/kg) aggravated scopolamine‐ and diabetes‐induced learning and memory deficit. Co‐administration of L‐NAME (20 mg/kg) after TAD (20 mg/kg) produced significant increase in cognitive performance as compared to scopolamine‐ and diabetic‐ control group. This showed that L‐NAME (20 mg/kg) aggravated scopolamine‐ and diabetes‐induced learning and memory deficit was significantly reversed by TAD (20 mg/kg). The results of the present study revealed that tadalafil by inhibiting PDE5 possibly elevated the cGMP level that through a diversity of its substrates produced neuropharmacological effects in cognitive dysfunction.

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ADMET considerations for phosphodiesterase-5 inhibitors

Cited by 19 publications

References 111 publications

Cellular and molecular mechanisms of pentoxifylline's beneficial effects in experimental polycystic ovary

Cellular and molecular mechanisms of pentoxifylline's beneficial effects in experimental polycystic ovary

Significance of Ligand-Anchored Polymers for Drug Targeting in the Treatment of Colonic Disorders

Improvement of cognitive dysfunction by a novel phosphodiesterase type 5 inhibitor, Tadalafil

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