InhibitionApremilastMediatorsSelective inhibitorsDiseasesAnti-inflammatory activityAngiotensin converEnzymesSynthase inhibitorPDE3CyclooxygenaseNonsteroidalRecurrent inflammatory skinInhibitsTherapeuticPsoriasisSignificantlySelectivelyDecreasesPDEsAirwaysNeuroprotectiveAntagonistBowel DiseasePsoriaticCardiovascularTypeDermatologicalDrugsCytokinesDoseUstekinumabCOPDBiologicsMonotherapyTreatmentsCaffeineEfficacyDiseaseArthritisRolipramAsthmaMechanismsPatientsAgents
Inhibition10
- Ibudilast (development codes: AV-411 or MN-166) is an anti-inflammatory drug used mainly in Japan, which acts as a phosphodiesterase inhibitor, inhibiting the PDE4 subtype to the greatest extent, but also showing significant inhibition of other PDE subtypes. (wikipedia.org)
- phosphodiesterase 4 inhibitors significantly elevated cAMP and enhanced alcohol-mediated inhibition of dust-stimulated TNF-a release. (cdc.gov)
- This dual inhibition enables it to combine both bronchodilator and anti-inflammatory effects in one compound. (wraltechwire.com)
- We did a non-systematic analysis of literature on phosphodiesterase inhibition followed by a review of published information on apremilast and topical AN2728 and their use for psoriasis and atopic dermatitis. (escholarship.org)
- It was recognised that papaverine and pentoxifylline mediated vasorelaxation by a number of mechanisms including non-selective PDE inhibition and these drugs can be considered as forerunners to the clinically successful PDE5 inhibitors used today for the treatment of erectile dysfunction. (biomedjournal.com)
- It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. (lookformedical.com)
- The inhibition of PDE4 enzyme produces anti-inflammatory and bronchodilator effects in the lung by inducing an increase in cAMP concentrations. (bvsalud.org)
- The selective inhibition of the phosphodiesterase 4B (PDE4B) subtype may represent an intriguing technique for combating this highly contagious disease with fewer side effects. (bvsalud.org)
- 13 Some other major metabolites, M14 and M16, are significantly less active in the inhibition of PDE4 and inflammatory mediators than their parent drug, apremilast. (drugbank.com)
- Its weak anti-inflammatory activity is related to inhibition of prostaglandin synthesis in the CNS. (medicscientist.com)
Apremilast5
- Apremilast is a non-steroidal drug, phosphodiesterase type 4 (PDE-4) inhibitor, used for the treatment of inflammatory conditions such as psoriasis and psoriatic arthritis. (e-lactancia.org)
- Therefore, we conducted experiments focusing on the antifibrotic and anti-inflammatory effects of apremilast using dermal fibroblasts derived from patients with SSc and an SSc mouse model. (bvsalud.org)
- Apremilast, also known as Otezla, is a phosphodiesterase 4 (PDE4) inhibitor used to treat various types of symptoms resulting from certain inflammatory autoimmune diseases. (drugbank.com)
- Apremilast reduces but does not completely inhibit various inflammatory cytokines such as IL-1α, IL-6, IL-8, IL-10 MCP-1, MIP-1β, MMP-3, and TNF-α, relieving the symptoms of psoriasis and Behcet's disease, which are caused by an increase in these inflammatory mediators. (drugbank.com)
- The full mechanism of action of this drug is not fully established, however, it is known that apremilast is an inhibitor of phosphodiesterase 4 (PDE4), which mediates the activity of cyclic adenosine monophosphate (cAMP), a second messenger. (drugbank.com)
Mediators6
- Simultaneous exposure to hog barn dust and alcohol decreases inflammatory mediators, TNF-a, IL-6, and IL-8, in mice. (cdc.gov)
- In addition, as COPD results from inflammation and/or alterations in repair mechanisms, the "spill-over" of inflammatory mediators into the circulation may result in important systemic manifestations of the disease, such as skeletal muscle wasting and cachexia. (ersjournals.com)
- PDE4 is an enzyme that increases production of pro-inflammatory mediators and decreases production of anti-inflammatory mediators. (medscape.com)
- Nycomed's Daxas is an orally administered phosphodiesterase 4 (PDE4) enzyme inhibitor targeting cells and mediators in the body believed to be important in the COPD disease process. (worldpharmanews.com)
- 14 An increase in cAMP results in the suppression of inflammation by decreasing the expression of TNF-α, IL-17, IL-23, and other inflammatory mediators. (drugbank.com)
- The above inflammatory mediators have been implicated in various psoriatic conditions as well as Behcet's disease, leading to their undesirable inflammatory symptoms such as mouth ulcers, skin lesions, and arthritis. (drugbank.com)
Selective inhibitors3
- By increasing our understanding of the physiological roles of the individual PDE isoforms, in parallel with the development of even more selective inhibitors of these enzymes, it is highly likely that better therapeutically active drugs will emerge. (biomedjournal.com)
- Taking into account that the increase in cAMP levels has an important impact on immunosuppressive and anti-inflammatory properties, selective inhibitors of PDEs have been widely studied for the treatment of certain pathologies such as immunological disorders, inflammatory processes and disorders of the central nervous system. (justia.com)
- Piclamilast and rolipram are known selective inhibitors of PDE4, which are unfortunately endowed with common side effects, such as nausea and emesis. (bvsalud.org)
Diseases13
- and HPP737, an orally administered non-CNS penetrant phosphodiesterase type 4 (PDE4) inhibitor that addresses inflammatory diseases and psoriasis. (etfdailynews.com)
- Spondyloarthropathies (SpA) encompass a group of chronic inflammatory diseases sharing common genetic and clinical features, including the association with HLA-B27 antigen, the involvement of both the axial and the peripheral skeleton, the presence of dactylitis, enthesitis, and typical extra-articular manifestations such as psoriasis, inflammatory bowel disease, and acute anterior uveitis (AAU). (hindawi.com)
- Spondyloarthropathies (SpA) embrace different chronic inflammatory diseases sharing common genetic (association with HLA-B27 antigen) and clinical features. (hindawi.com)
- Phosphodiesterase inhibitors constitute a widely used class of drugs that may see growing use for inflammatory dermatologic diseases. (escholarship.org)
- The pathogenesis of vitiligo is unknown, but an autoimmune hypothesis prevails and is supported by several factors: Its association with other autoimmune diseases, the high level of antibodies against melanocytes found in 10% of patients with vitiligo, susceptibility loci associated with vitiligo found in genome-wide association studies that encode immunomodulatory proteins, and lastly, an inflammatory infiltrate that is observed at the margin of active lesions ( 11 , 12 ). (spandidos-publications.com)
- Daxas is expected to act on the underlying mechanism of COPD and related inflammatory diseases. (worldpharmanews.com)
- Nycomed is a privately owned global pharmaceutical company with a differentiated portfolio focused on branded medicines in gastroenterology, respiratory and inflammatory diseases, pain, osteoporosis and tissue management. (worldpharmanews.com)
- The present invention relates to a family of S-substituted quinazoline derivatives that inhibitors of the enzyme phosphodiesterase 7 (PDE7), useful for the treatment or prevention of diseases mediated by said enzyme, especially inflammatory, neurodegenerative, neurological, psychiatric and/or autoimmune diseases. (justia.com)
- The S-substituted quinazoline derivatives of the present invention are, therefore, useful for the treatment or prevention of diseases mediated by said enzyme PDE7, especially inflammatory, neurodegenerative, neurological, psychiatric and/or autoimmune diseases. (justia.com)
- Patent application PCT WO2008/113881 discloses a family of compounds with a quinazoline nucleus that have dual inhibitory activity of enzymes PDE7 and PDE4 and are useful for the treatment of inflammatory or autoimmune diseases. (justia.com)
- The robust anti-inflammatory effects of glucocorticoids are applied broadly in the clinical setting to treat diverse conditions, including rheumatic diseases, allergy, skin disorders, pulmonary conditions, cancer, transplant rejection, and even spinal cord injury. (biomedcentral.com)
- After the demise of Merck's PDE-IV inhibitor (licensed from Celltech Group) in April 2003, Ariflo has emerged as the frontrunner in this new class of agents for inflammatory airways diseases, such as COPD. (clinicaltrialsarena.com)
- PDE-IV is the predominant phosphodiesterase isoenzyme in respiratory tissues and is therefore a suitable target for therapy of inflammatory airways diseases such as COPD. (clinicaltrialsarena.com)
Anti-inflammatory activity5
- An alternative to this medicinal chemistry approach is a systems biology based strategy that seeks to amplify selectively the anti-inflammatory activity of very low dose glucocorticoid in immune cells without modulating alternative cellular networks that mediate glucocorticoid toxicity. (biomedcentral.com)
- The combination of prednisolone and the antithrombotic drug dipyridamole was profiled using in vitro and in vivo models of anti-inflammatory activity and glucocorticoid-induced adverse effects to demonstrate a dissociated activity profile. (biomedcentral.com)
- In rat models of acute lipopolysaccharide-induced endotoxemia and delayed-type hypersensitivity, and in chronic models of collagen-induced and adjuvant-induced arthritis, the combination produced anti-inflammatory activity that required only a subtherapeutic dose of prednisolone. (biomedcentral.com)
- The immune-specific amplification of prednisolone anti-inflammatory activity by dipyridamole did not extend to glucocorticoid-mediated adverse effects, including corticosterone suppression or increased expression of tyrosine aminotransferase, in vivo after repeat dosing in rats. (biomedcentral.com)
- Compound D50 has shown strong anti-inflammatory activity, as evidenced by experimental results. (bvsalud.org)
Angiotensin conver3
- Perindopril belongs to the class of medications called angiotensin converting enzyme (ACE) inhibitors. (medbroadcast.com)
- It is often taken with a diuretic (water pill) and an angiotensin converting enzyme (ACE) inhibitor. (medbroadcast.com)
- Telmisartan is also used to reduce the risk of death caused by a heart attack or stroke, for people who cannot use another type of medication called angiotensin-converting enzyme inhibitor . (pharmasave.com)
Enzymes3
- RPL554 is a first-in-class, inhaled, dual inhibitor of the enzymes phosphodiesterase 3 and 4 designed to have anti-inflammatory as well as bronchodilator properties. (pharmatimes.com)
- The phosphodiesterases (PDEs) are a family of metal-dependent phosphohydrolase enzymes that metabolise the second messengers adenosine 3′,5′-cyclic monophosphate and guanosine 3′,5′-cyclic monophosphate (cAMP and cGMP) to their respective 5′-monophosphates. (justia.com)
- The phosphodiesterases are enzymes responsible for hydrolysis of cyclic adenosine monophosphate (cAMP), a naturally occurring substance that mediates suppression of inflammatory cell activation. (clinicaltrialsarena.com)
Synthase inhibitor1
- In addition, the NO synthase inhibitor, l-NMMA, also reversed the alcohol-blocking effect on dust-stimulated TNF-a. (cdc.gov)
PDE34
- PDE3 inhibitors can be thought of as a backdoor approach to cardiac stimulation, whereas β-agonists go through the front door to produce the same cardiac effects. (biomedjournal.com)
- PDE3 was identified as a potential therapeutic target in cardiovascular disease and asthma, and indeed, PDE3 inhibitors have subsequently been shown to relax vascular and airway smooth muscle, inhibit platelet aggregation and induce lipolysis. (biomedjournal.com)
- In respect to cAMP-dependent transcription, inhibitors of PDE3 (siguazodan, cilostazol) and PDE4 (rolipram, GSK256066, roflumilast N -oxide) each sensitized to the LABA, formoterol. (aspetjournals.org)
- Collectively, these data provide a rationale for the use of PDE3 and PDE4 inhibitors in the treatment of COPD and asthma where they may enhance, sensitize, and prolong the effects of LABA/ICS combination therapies. (aspetjournals.org)
Cyclooxygenase1
- inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which is responsible for prostaglandin synthesis. (medscape.com)
Nonsteroidal3
- Crisaborole is a first-in-class, nonsteroidal, topical anti- inflammatory , PDE inhibitor approved for the treatment of mild to moderate atopic dermatitis . (dermnetnz.org)
- Treat individuals with arthritis and musculoskeletal pain with nonsteroidal anti-inflammatory drugs (NSAIDs). (medscape.com)
- Synthetic disease-modifying antirheumatic drugs, including methotrexate, sulfasalazine, and leflunomide, are currently the initial therapy after failure of nonsteroidal anti-inflammatory drugs and local therapy for active disease. (medscape.com)
Recurrent inflammatory skin2
- Pediatric atopic dermatitis is a chronic, recurrent inflammatory skin condition that can negatively impact the quality of life of the child and family or caregivers. (whnt.com)
- Seborrheic dermatitis is a common, chronic, and recurrent inflammatory skin disease that causes red patches covered with large, greasy, flaking scales, and persistent itch. (medscape.com)
Inhibits3
- METHODS: Because we recently demonstrated that PKA activation inhibits the TNF-a sheddase, TNF-a-converting enzyme (TACE), we hypothesized that an alcohol-mediated PKA pathway blocks TACE activity and prevents the normative inflammatory response to hog barn dust exposure. (cdc.gov)
- It is a non-steroidal topical monotherapy that inhibits the phosphodiesterase (PDE)-4 enzyme in the skin. (dermnetnz.org)
- Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLYL CYCLASES and cyclic AMP. (lookformedical.com)
Therapeutic4
- Phosphodiesterase inhibitors (PDIs) have important vascular and myocardial protective effects and thus have shown therapeutic usefulness in the clinical settings for treatment of patients with heart failure, pulmonary hypertension, and coronary artery disease. (biomedjournal.com)
- The potential activity for selective phosphodiesterase inhibitors as therapeutic agents was predicted as early as 1977 by Weiss and Hait (Weiss and Hait, 1977). (biomedjournal.com)
- Previous efforts to design glucocorticoid structures with an increased therapeutic window have focused on dissociating anti-inflammatory transcriptional repression from adverse effects primarily driven by transcriptional activation. (biomedcentral.com)
- These data suggest that the multi-target mechanism of low-dose prednisolone and dipyridamole creates a dissociated activity profile with an increased therapeutic window through cellular network selective amplification of glucocorticoid-mediated anti-inflammatory signaling. (biomedcentral.com)
Psoriasis3
- Psoriasis, which manifests most often as plaque psoriasis, is a chronic, relapsing, inflammatory skin disorder with a strong genetic basis. (medscape.com)
- The disease course is usually complicated by extra-articular manifestations (EAMs), such as psoriasis, inflammatory bowel disease (IBD), and acute anterior uveitis (AAU) [ 2 ]. (hindawi.com)
- Zhongmei will have rights to cream and foam formulations of roflumilast, a next-gen phosphodiesterase type 4 (PDE4) inhibitor for dermatological conditions including plaque psoriasis, seborrheic dermatitis and atopic dermatitis. (chinabiotoday.com)
Significantly3
- The soluble adenylyl cyclase inhibitor, KH7, however, significantly increased the inflammatory response to hog barn dust. (cdc.gov)
- The present invention relates to a family of S-substituted quinazoline derivatives that have selective or specific inhibitory activity of the enzyme phosphodiesterase 7 (PDE7), without significantly inhibiting other phosphodiesterases such as the enzyme phosphodiesterase 4 (PDE4). (justia.com)
- The inventors of the present patent, after extensive and exhaustive research, have surprisingly discovered a family of S-substituted quinazoline derivatives that have selective or specific inhibitory activity of the enzyme phosphodiesterase 7 (PDE7), without significantly inhibiting other phosphodiesterases such as the enzyme phosphodiesterase 4 (PDE4). (justia.com)
Selectively1
- A phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase (PDE) selectively in the brain. (biomedjournal.com)
Decreases1
- Colchicine decreases leukocyte motility and phagocytosis in inflammatory responses. (medscape.com)
PDEs2
- The homeostatic role of phosphodiesterases (PDEs) as related to the intracellular levels of cAMP and cGMP was first described by Sutherland (Sutherland, Rall, 1958) who, due to this, was awarded the Nobel Prize for Physiology and Medicine in 1971. (biomedjournal.com)
- Phosphodiesterases (PDEs) hydrolyze the phosphodiester bond of cAMP and cGMP to form the inactive 5′-AMP and 5′-GMP. (biomedjournal.com)
Airways2
- Asthma is a chronic inflammatory disease of the airways that affects over 300 million individuals worldwide [ 1 ]. (biomedcentral.com)
- Congestive heart failure Inflammatory airways disease. (biomedjournal.com)
Neuroprotective1
- The anti-Parkinson drug rasagiline an irreversible and selective monoamine oxidase (MAO)-B inhibitor, was shown to possess neuroprotective activities, involving multiple survival pathways among them the up-regulation of protein kinase C (PKC)alpha, PKCepsilon, the anti-apoptotic Bcl-2, Bcl-xL, and Bcl-w and the induction of brain-derived- and glial cell line-derived neurotrophic factors (BDNF, GDNF). (illnesshacker.com)
Antagonist1
- Ibudilast is principally a PDE4 inhibitor but has also been shown to act as an antagonist at the toll-like receptor 4 (TLR4). (wikipedia.org)
Bowel Disease1
- In the last few decades, a better knowledge of the inflammatory pathways involved in the pathogenesis of Inflammatory Bowel Disease (IBD) has promoted biological therapy as an important tool to treat IBD patients. (mdpi.com)
Psoriatic2
- The aim of this study was to systemically review the efficacy and safety of inhibitors of interleukin 6 (IL-6): clazakizumab, IL-12/23: ustekinumab, and IL-17A: secukinumab, brodalumab, and ixekizumab in psoriatic arthritis (PsA). (medscape.com)
- Psoriatic arthritis (PsA) is an inflammatory arthritis with no gender preference and has an estimated incidence of 6 per 100,000 per year and a prevalence of 1 to 2 per 1000 in the general population. (medscape.com)
Cardiovascular1
- Table 1 summarizes the functions of each PDE and the cardiovascular effects of specific inhibitors. (biomedjournal.com)
Type3
- We present the first three reported cases of thromboangiitis obliterans successfully treated with phosphodiesterase type 5 inhibitors, followed by a discussion of the rationale for the use of these agents in thromboangiitis obliterans. (nih.gov)
- The manufacturer, Arcutis Biotherapeutics, is developing topical cream and foam formulations of roflumilast, a highly potent and selective phosphodiesterase type 4 (PDE4) inhibitor for use in treating inflammatory dermatoses, particularly in areas of the body with hair such as the scalp, face, and trunk. (medscape.com)
- With broad anti-inflammatory properties, orismilast is a next-generation phosphodiesterase type-4 (PDE4) inhibitor. (clinicaltrialsarena.com)
Dermatological1
- Specific phosphodiesterase inhibitors with anti-inflammatory properties are being assessed as dermatological treatments. (escholarship.org)
Drugs6
- This likely plays a large part in its effect, specifically its synergy with opioid drugs, its anti-inflammatory effect, and its own painkilling effect. (wikipedia.org)
- However, new broad-spectrum anti-inflammatory treatments, such as phosphodiesterase 4 inhibitors, have significant side-effects so it may be necessary to develop inhaled drugs in the future. (ersjournals.com)
- The management of SpA has dramatically improved over the last decades due to the development of new treat-to-target strategies and to the introduction of biologic disease modifying antirheumatic drugs (bDMARDs), particularly tumor necrosis factor alpha inhibitors (TNFis), currently used for the treatment of nonresponder patients to conventional synthetic agents. (hindawi.com)
- Among biologic disease modifying antirheumatic drugs (bDMARDs), tumor necrosis factor alpha inhibitors (TNFis) are currently widely used for the treatment of SpA. (hindawi.com)
- Phosphodiesterase inhibitors are commonly used drugs. (escholarship.org)
- By inhibiting PDE-IV, drugs such as Ariflo increase levels of cAMP and reduce inflammatory cell activation in the respiratory tract. (clinicaltrialsarena.com)
Cytokines1
- These include biological agents targeting pro-inflammatory cytokines such as interleukin-5 and interleukin-13, inhaled ultra long-acting β 2 -agonists and once daily inhaled corticosteroids. (biomedcentral.com)
Dose1
- Switching to an alternative TNF-α inhibitor or increasing the dose or frequency of administration may sometimes overcome this problem. (medscape.com)
Ustekinumab2
- Eight studies including 2722 subjects demonstrate the efficacy of IL inhibitors clazakizumab, secukinumab, ixekizumab, brodalumab, and ustekinumab in the treatment of PsA. (medscape.com)
- Our meta-analysis shows that the inhibitors of IL-6 (clazakizumab), IL-12/23 (ustekinumab), and IL-17A (secukinumab, brodalumab, ixekizumab) are efficacious and generally well tolerated when used to treat patients with PsA. (medscape.com)
COPD3
- For many, they are the result of a systemic "spill-over" of the inflammatory and reparatory events occurring in the lungs of patients with COPD, with the disease remaining at the centre of the process (fig. 1 ⇓ ), whereas for others the pulmonary manifestations of COPD are one more form of expression of a "systemic" inflammatory state with multiple organ compromise 3 , 4 . (ersjournals.com)
- Chronic Obstructive Pulmonary Disease (COPD) Chronic obstructive pulmonary disease (COPD) is airflow limitation caused by an inflammatory response to inhaled toxins, often cigarette smoke. (msdmanuals.com)
- Selective PDE-IV inhibitors are seen as a potentially important new class of agents for COPD. (clinicaltrialsarena.com)
Biologics1
- [ 6 ] The advent of biologics, including tumor necrosis factor α (TNF-α) inhibitors, has advanced the treatment of PsA. (medscape.com)
Monotherapy1
- It is an irreversible inhibitor of monoamine oxidase and is used as a monotherapy in early Parkinson's disease or as an adjunct therapy in more advanced cases. (illnesshacker.com)
Treatments1
- The limitations of this paper are the limited number of published studies, the lack of long-term data, and the lack of head -to - head trials directly comparing phosphodiesterase inhibitors with other treatments. (escholarship.org)
Caffeine1
- Caffeine, a methylxanthine, is a phosphodiesterase inhibitor. (medicscientist.com)
Efficacy3
- These medications have analgesic and anti-inflammatory properties to treat arthralgia and arthritis and are available with slightly different safety and efficacy profiles. (medscape.com)
- We included randomized controlled trials that assessed the efficacy of IL inhibitors and reported American College of Rheumatology 20 response at 24 weeks. (medscape.com)
- [ 6-9 ] However, TNF-α inhibitors may also have primary inefficacy or lose efficacy with time in some patients. (medscape.com)
Disease2
- Thromboangiitis obliterans, or Buerger's disease, is a non-atherosclerotic, segmental, inflammatory disease affecting the small- and medium-sized vessels of the distal extremities. (nih.gov)
- Selective PDE-IV inhibitors, such as Ariflo, have potential to not only target symptoms of the disease but to also ameliorate the underlying components of airway obstruction and inflammation. (clinicaltrialsarena.com)
Arthritis1
- The principal symptoms are inflammatory chronic back pain, peripheral arthritis (typically asymmetric monoarthritis or oligoarthritis predominantly affecting the joints of the lower extremities), dactylitis, and enthesitis [ 1 ]. (hindawi.com)
Rolipram1
- Siguazodan plus rolipram was also more effective at inducing cAMP-dependent transcription than either inhibitor alone. (aspetjournals.org)
Asthma1
- This mini-review focuses on biological agents, new inhaled long-acting bronchodilators and corticosteroids, arachidonic acid pathway blockers, bronchial thermoplasty plus a range of other anti-inflammatory agents that have been recently licensed or are at an advanced stage of development for patients with severe asthma (Figure 1 ). (biomedcentral.com)
Mechanisms1
- Glucocorticoids, also known as corticosteroids, induce effector gene transcription as a part of their anti-inflammatory mechanisms of action. (aspetjournals.org)
Patients2
- London, UK-based Verona Pharma's experimental phosphodiesterase therapy has hit targets in a mid-stage trial in patients with cystic fibrosis. (pharmatimes.com)
- Despite many improvements in CPB technology and circuit design, patients still undergo an intense inflammatory response when their blood comes in contact with the nonendothelial surfaces involved in extracorporeal circulation. (medscape.com)
Agents1
- The Khamisiyah ammunition storage that housed chemical warfare agents such as sarin, an acetylcholinesterase (AChE) inhibitor, was demolished during the GW, releasing toxicants into the atmosphere affecting deployed troops. (cdc.gov)