Editing Phosphodiesterase inhibitor (section)

===PDE4 selective inhibitors===
[[File:PDE4-inhibiting thalidomide analogs.svg|thumb|PDE4 inhibitors]]
{{main|PDE4 inhibitor}}
*[[Mesembrenone]], an alkaloid from the herb ''[[Sceletium tortuosum]]''
*[[Rolipram]], used as investigative tool in pharmacological research
*[[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.
*[[Piclamilast]], a more potent inhibitor than rolipram.<ref name="Piclamilast-Walther">{{cite journal | vauthors =de Visser YP, Walther FJ, Laghmani EH, van Wijngaarden S, Nieuwland K, Wagenaar GT | title=Phosphodiesterase-4 inhibition attenuates pulmonary inflammation in neonatal lung injury | journal=Eur Respir J | year=2008 | pages=633–644 | volume=31 | issue=3 | pmid=18094015 | doi=10.1183/09031936.00071307 | doi-access=free }}</ref>
*[[Luteolin]], supplement extracted from peanuts that also possesses [[IGF-1]] properties.<ref name="Luteolin-Yu">{{cite journal | vauthors =Yu MC, Chen JH, Lai CY, Han CY, Ko WC | title=Luteolin, a non-selective competitive inhibitor of phosphodiesterases 1–5, displaced [(3)H]-rolipram from high-affinity rolipram binding sites and reversed xylazine/ketamine-induced anesthesia | journal=Eur J Pharmacol | year=2009 | pages=269–75 | volume=627 | issue=1–3 | pmid=19853596 | doi=10.1016/j.ejphar.2009.10.031 }}</ref>
*[[Drotaverine]], used to alleviate renal colic pain, also to hasten cervical dilatation in labor
*[[Roflumilast]], indicated for people with severe COPD to prevent symptoms such as coughing and excess mucus from worsening<ref>{{cite web|url=http://pharmacistsociety.skipta.com/article.aspx/o/4c18ca7f-1da9-4587-b304-64014e651663/09b6025d-60a0-4657-8b3f-b78ffc8f6f1c|title=Powered by Skipta technology, PharmacistSociety.com is the social network for verified Pharmacists to communicate and collaborate.|website=pharmacistsociety.skipta.com|access-date=1 May 2018|url-status=dead|archive-url=https://web.archive.org/web/20120419174156/http://pharmacistsociety.skipta.com/article.aspx/o/4c18ca7f-1da9-4587-b304-64014e651663/09b6025d-60a0-4657-8b3f-b78ffc8f6f1c|archive-date=19 April 2012}}</ref>
*[[Apremilast]], used to treat psoriasis and psoriatic arthritis.
*[[Crisaborole]], used to treat atopic dermatitis.
*[[Glaucine]], an [[aporphine]] alkaloid, low-potency PDE4 inhibitor, [[calcium channel blocker]], [[dopamine antagonist]] and [[5-HT2A]] positive allosteric modulator, used as [[antitussive]] in Eastern Europe and Iceland.

PDE4 is the major cAMP-metabolizing enzyme found in inflammatory and immune cells. PDE4 inhibitors have proven potential as anti-inflammatory drugs, especially in inflammatory [[pulmonary disease]]s such as [[asthma]], [[Chronic obstructive pulmonary disease|COPD]], and [[rhinitis]]. They suppress the release of [[cytokine]]s and other inflammatory signals, and inhibit the production of reactive oxygen species. PDE4 inhibitors may have [[antidepressive]] effects<ref name="Antidepressant-Bobon">{{cite journal | vauthors =Bobon D, Breulet M, Gerard-Vandenhove MA, Guiot-Goffioul F, Plomteux G, Sastre-y-Hernandez M, Schratzer M, Troisfontaines B, von Frenckell R, Wachtel H | title=Is phosphodiesterase inhibition a new mechanism of antidepressant action? A double blind double-dummy study between rolipram and desipramine in hospitalized major and/or endogenous depressives | journal=Eur Arch Psychiatry Neurol Sci | year=1988 | pages=2–6 | volume=238 | issue=1 | pmid=3063534 | doi=10.1007/BF00381071 | s2cid=7795640 }}</ref> and have also been proposed for use as [[antipsychotic]]s.<ref name="Antipsychotic-Maxwell">{{cite journal | vauthors =Maxwell CR, Kanes SJ, Abel T, Siegel SJ | title=Phosphodiesterase inhibitors: a novel mechanism for receptor-independent antipsychotic medications | journal=Neuroscience | year=2004 | pages=101–7 | volume=129 | issue=1 | pmid=15489033 | doi = 10.1016/j.neuroscience.2004.07.038 | s2cid=19578277 }}</ref><ref name="Antipsychotic-Kanes">{{cite journal | vauthors =Kanes SJ, Tokarczyk J, Siegel SJ, Bilker W, Abel T, Kelly MP | title=Rolipram: A specific phosphodiesterase 4 inhibitor with potential antipsychotic activity | journal=Neuroscience | year=2006 | pages=239–46 | volume=144 | issue=1 | pmid=17081698 | doi=10.1016/j.neuroscience.2006.09.026 | pmc=3313447}}</ref>

On October 26, 2009, the [[University of Pennsylvania]] reported that researchers at their institution had discovered a link between elevated levels of PDE4 (and therefore decreased levels of cAMP) in sleep deprived mice. Treatment with a PDE4 inhibitor raised the deficient cAMP levels and restored some functionality to hippocampus-based memory functions.<ref name="Sleep-UniPenn">{{cite journal | vauthors =Vecsey CG, Baillie GS, Jaganath D, Havekes R, Daniels A, Wimmer M, Huang T, Brown KM, Li XY, Descalzi G, Kim SS, Chen T, Shang YZ, Zhuo M, Houslay MD, Abel T | title=Sleep deprivation impairs cAMP signaling in the hippocampus | journal=Nature | year=2009 | pages=1122–1125 | volume=461 | issue=7267 | pmid=19847264 | doi=10.1038/nature08488 | pmc=2783639 | bibcode=2009Natur.461.1122V }}</ref>