Phosphodiesterase-4 inhibitor

Source: Wikipedia, the free encyclopedia.
(Redirected from
PDE4 inhibitor
)
Rolipram, the prototypical PDE4 inhibitor

A phosphodiesterase-4 inhibitor, commonly referred to as a PDE4 inhibitor, is a drug used to block the degradative action of

immune cells. They are predominantly responsible for hydrolyzing cAMP within both immune cells and cells in the central nervous system.[1]

Therapeutic utility

The prototypical PDE4 inhibitor is

long term memory-improving),[2] wakefulness-promoting,[3] neuroprotective,[4][5] and anti-inflammatory effects.[6]
Consequently, PDE4 inhibitors have been investigated as treatments for a diverse group of different diseases, including central nervous system disorders such as
autism and inflammatory conditions such as chronic obstructive pulmonary disease (COPD), asthma and rheumatoid arthritis.[12][13][14]

PDE4D inhibition, along with

frontal cortex, which may contribute to the antipsychotic and procognitive effects of PDE4 inhibitors.[16] Whereas PDE4C is expressed primarily in the periphery and hence may be partly responsible for the peripheral effects of PDE4 inhibitors (e.g. their anti-inflammatory effects).[14] PDE4 inhibition is also known to attenuate ethanol seeking and consumption in rats,[17] hence suggesting its possible utility in the treatment of alcohol dependence. Indeed, one experiment has found that intake of a PDE4 oral medication for psoriasis has significantly reduced alcohol consumption in serious human drinkers compared with those taking the placebo.[18] A few different lines of evidence suggests the therapeutic utility in the treatment of brain tumours.[19]

The clinical development of PDE4 inhibitors has been hampered by their potent emetic effects, which appear to be related to their inhibition of PDE4D which is expressed in the area postrema.[14]

Adverse reactions

Nausea, vomiting, and related general gastrointestinal side effects are the most commonly implicated side effects of PDE4 inhibitors. Other possible side effects include respiratory and urinary tract infections, which have been discovered from the clinical use of roflumilast.[20]

Examples

See also: List of phosphodiesterase inhibitors
  • plaque psoriasis under the brand name Otezla.[22]
  • GlaxoSmithKline for treatment of COPD.[23]
  • Crisaborole (AN2728), a boron-containing drug for the topical treatment of psoriasis and atopic dermatitis.[24][25] It was approved by the FDA on December 14, 2016 under the brand name Eucrisa for the treatment of mild-to-moderate atopic dermatitis (eczema) in patients 2 years of age and older.[26]
  • Caffeine is a weak, non-selective PDE inhibitor.[27] A metabolite of caffeine, theophylline, is a more potent PDE inhibitor.[27]
  • Diazepam, a benzodiazepine anxiolytic, amnesic, hypnotic, sedative and muscle relaxant.[28]
  • antitussive
    in Eastern Europe and Iceland.
  • Ibudilast, a neuroprotective and bronchodilator drug used mainly in the treatment of asthma and stroke. It inhibits PDE4 to the greatest extent, but also shows significant inhibition of other PDE subtypes, and so acts as a selective PDE4 inhibitor or a non-selective phosphodiesterase inhibitor, depending on the dose.
  • IGF-1 properties.[29]
  • Sceletium tortuosum
    (Kanna).
  • Piclamilast, a more potent inhibitor than rolipram.[30]
  • plaque psoriasis under the brand name Zoryve.[31]
  • Rolipram, used as investigative tool in pharmacological research.
  • Sceletium tortuosum
    (kanna).

Mode of action

PDE4 hydrolyzes cyclic adenosine monophosphate (cAMP) to inactive adenosine monophosphate (AMP). Inhibition of PDE4 blocks hydrolysis of cAMP, thereby increasing levels of cAMP within cells.[citation needed]

See also

  • Development of analogs of thalidomide
  • Forskolin

References

  1. PMID 18660825
    .
  2. PMID 9844008
    .
  3. S2CID 37020086
    .
  4. S2CID 2768440
    .
  5. S2CID 25453633
    .
  6. ^ "Intracellular Mechanisms of Inflammation:PDE4 Promotes the Release of Proinflammatory Mediators". Celgene Corporation. 2012. Archived from the original on 2019-08-13. Retrieved 2012-07-24.
  7. S2CID 19578277
    .
  8. PMID 17081698
    .
  9. ^ Beal, MF; Cleren, C; Calingasan, NY; Yang, L; Klivenyi, P; Lorenzl, S (2005). "Oxidative Damage in Parkinson's Disease". U.S. Army Medical Research and Material Command Fort Detrick, Maryland 21702-5012. Archived from the original on May 23, 2012.
  10. PMID 19805389
    .
  11. S2CID 23444101
    .
  12. S2CID 22623399
    .
  13. ^
    PMID 17933689
    .
  14. ^
    ISBN 978-3-642-17968-6. [dead link
    ]
  15. S2CID 32661995
    .
  16. PMID 21833500
    .
  17. PMID 22671516
    .
  18. ^ Wilson, C. (2021). Psoriasis drug may cut alcohol misuse. New Scientist, 250(3340), p.16
  19. PMID 21450351
    .
  20. ^ a b "DALIRESP (roflumilast) tablet [Forest Laboratories, Inc.]". DailyMed. Forest Laboratories, Inc. August 2013. Retrieved 13 November 2013.
  21. ^ Brooks, M (21 March 2014). "FDA Clears Apremilast (Otezla) for Psoriatic Arthritis". Medscape Medical News. WebMD. Retrieved 28 March 2014.
  22. ^ Lowes, R (23 September 2014). "FDA Approves Apremilast (Otezla) for Plaque Psoriasis". Medscape Medical News. WebMD. Retrieved 13 October 2014.
  23. S2CID 2216800
    .
  24. PMID 19876791
    .
  25. PMID 24852768
    .
  26. ^ "FDA Approves Eucrisa for Eczema". U.S. Food and Drug Administration. 14 December 2016.
  27. ^
    PMID 16402111
    .
  28. PMID 9559885
    .
  29. PMID 19853596
    .
  30. PMID 18094015
    .
  31. ^ "FDA Approves Arcutis' Zoryve (Roflumilast) Cream 0.3% For the Treatment of Plaque Psoriasis in Individuals Age 12 and Older" (Press release). Arcutis Biotherapeutics. 29 July 2022. Archived from the original on 1 August 2022. Retrieved 1 August 2022 – via GlobeNewswire.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Phosphodiesterase-4_inhibitor&oldid=1184620767"