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			{{Short description|Chemical compound}}
	{{drugbox
			{{Drugbox
			| Verifiedfields = changed
	| Watchedfields = changed		| Watchedfields = changed
	| verifiedrevid = 308878953		| verifiedrevid = 464383368
	| drug_name=Rolipram
	| IUPAC_name = (''RS'')-4-(3-cyclopentyloxy-4-methoxy-phenyl)pyrrolidin-2-one		| IUPAC_name = (''RS'')-4-(3-cyclopentyloxy-4-methoxy-phenyl)pyrrolidin-2-one
	| image = rolipram.svg		| image = Rolipram.svg
		⚫	| width = 200
	| imagename = 1 : 1 mixture (racemate)
⚫	| width = 200px
			<!--Clinical data-->
	| CASNo_Ref = {{cascite}}
			| tradename =
⚫	| CAS_number = 61413-54-5
⚫	| ATC_prefix = none
⚫	| ATC_suffix =
⚫	| ATC_supplemental =
⚫	| PubChem = 5092
⚫	| DrugBank = EXPT00228
⚫	| C = 16 | H = 21 | N = 1 | O = 3
	| molecular_weight = 275.347 g/mol
	| bioavailability =
⚫	| protein_bound =
	| metabolism =
⚫	| elimination_half-life = 1-3 h
	| excretion =
	| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->		| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
	| pregnancy_US = <!-- A / B / C / D / X -->		| pregnancy_US = <!-- A / B / C / D / X -->
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	| legal_UK = <!-- GSL / P / POM / CD -->		| legal_UK = <!-- GSL / P / POM / CD -->
	| legal_US = <!-- OTC / Rx-only -->		| legal_US = <!-- OTC / Rx-only -->
	| legal_status =		| legal_status = Investigational
	| routes_of_administration =		| routes_of_administration =
			<!--Pharmacokinetic data-->
			| bioavailability = 75%<ref name = PK>{{cite journal | vauthors = Krause W, Kühne G, Sauerbrey N | title = Pharmacokinetics of (+)-rolipram and (-)-rolipram in healthy volunteers | journal = European Journal of Clinical Pharmacology | volume = 38 | issue = 1 | pages = 71–75 | year = 1990 | pmid = 2328751 | doi = 10.1007/BF00314807 | s2cid = 25683209 }}</ref>
		⚫	| protein_bound =
			| metabolism = ] via ], ], ] and ]<ref name = PK/>
		⚫	| elimination_half-life = 3 hours<ref name = PK/>
			| excretion = Urine (80%)<ref name = PK/>
			<!--Identifiers-->
			| IUPHAR_ligand = 5260
			| CAS_number_Ref = {{cascite|correct|??}}
		⚫	| CAS_number = 61413-54-5
		⚫	| ATC_prefix = none
		⚫	| ATC_suffix =
		⚫	| ATC_supplemental =
			| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
			| ChemSpiderID = 4913
			| ChEBI_Ref = {{ebicite|correct|EBI}}
			| ChEBI = 104872
			| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
			| StdInChI = 1S/C16H21NO3/c1-19-14-7-6-11(12-9-16(18)17-10-12)8-15(14)20-13-4-2-3-5-13/h6-8,12-13H,2-5,9-10H2,1H3,(H,17,18)
			| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
			| StdInChIKey = HJORMJIFDVBMOB-UHFFFAOYSA-N
		⚫	| PubChem = 5092
			| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
		⚫	| DrugBank = DB04149
			| UNII_Ref = {{fdacite|correct|FDA}}
			| UNII = K676NL63N7
			| ChEMBL_Ref = {{ebicite|correct|EBI}}
			| ChEMBL = 63
			| KEGG_Ref = {{keggcite|changed|kegg}}
			| KEGG = D01783
			<!--Chemical data-->
		⚫	| C=16 | H=21 | N=1 | O=3
			| smiles = COc1ccc(cc1OC1CCCC1)C1CNC(=O)C1
	}}		}}
			'''Rolipram''' is a selective ] discovered and developed by ] as a potential ] drug in the early 1990s.<ref name="Zhu 387–98">{{cite journal | vauthors = Zhu J, Mix E, Winblad B | title = The antidepressant and antiinflammatory effects of rolipram in the central nervous system | journal = CNS Drug Reviews | volume = 7 | issue = 4 | pages = 387–398 | date = Winter 2001 | pmid = 11830756 | pmc = 6741679 | doi = 10.1111/j.1527-3458.2001.tb00206.x }}</ref> It served as a prototype molecule for several companies' ] and development efforts.<ref name=McKenna>{{cite book | vauthors = McKenna JM, Muller GW | chapter = Chapter 33: Medicinal Chemistry of PDE4 Inhibitors. | title = Cyclic Nucleotide Phosphodiesterases in Health and Disease | veditors = Beavo J, Francis SH, Houslay MD | publisher = CRC Press | date = December 2006 | isbn = 9781420020847}}</ref>{{rp|668ff}} Rolipram was discontinued after clinical trials showed that its ] was too narrow; it could not be dosed at high enough levels to be effective without causing significant gastrointestinal side effects.<ref name=McKenna/>{{rp|668}}
	'''Rolipram''' is a ]. Like most PDE4-inhibitors, it is an anti-inflammatory drug.<ref name="Anti-inflammatory-Griswold">{{cite journal | author=Griswold DE, Webb EF, Breton J, White JR, Marshall PJ, Torphy TJ. | title=Effect of selective phosphodiesterase type IV inhibitor, rolipram, on fluid and cellular phases of inflammatory response | journal=Inflammation | year=1993 | pages=333–44 | volume=17 | issue=3 | pmid=7687237 | doi=10.1007/BF00918994}}</ref> Rolipram is being studied as a possible alternative to current ].<ref name="Antidepressant-Bobon">{{cite journal | author=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}}</ref><ref name="Potential-antidepressant-Wachtel">{{cite journal | author=Wachtel H. | title=Potential antidepressant activity of rolipram and other selective cyclic adenosine 3',5'-monophosphate phosphodiesterase inhibitors | journal=Neuropharmacology | year=1983 | pages=267–72 | volume=22 | issue=3 | pmid=6302550 | doi=10.1016/0028-3908(83)90239-3}}</ref> Recent studies show that rolipram may have ] effects.<ref name="Antipsychotic-Maxwell">{{cite journal | author=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}}</ref><ref name="Antipsychotic-Kanes">{{cite journal | author=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}}</ref> Other beneficial effects of rolipram are:
	* Improved long term memory<ref name="LTP-Barad">{{cite journal | author=Barad M, Bourtchouladze R, Winder DG, Golan H, Kandel E. | title=Rolipram, a type IV-specific phosphodiesterase inhibitor, facilitates the establishment of long-lasting long-term potentiation and improves memory | journal=Proceedings of the National Academy of Science of the USA. | year=1998 | pages=15020–5 | volume=95 | issue=25 | pmid=9844008 | doi=10.1073/pnas.95.25.15020 | pmc=24568}}</ref>
	* Increased wakefulness<ref name="Wakefulness-Lelkes">{{cite journal | author=Lelkes Z, Alföldi P, Erdos A, Benedek G. | title=Rolipram, an antidepressant that increases the availability of cAMP, transiently enhances wakefulness in rats | journal=Pharmacology, Biochemistry and Behaviour | year=1998 | pages=835–9 | volume=60 | issue=4 | pmid=9700966 | doi=10.1016/S0091-3057(98)00038-0}}</ref>
	* Increased ]<ref name="Rolipram-Neuroprotection-Block">{{cite journal | author=Block F, Schmidt W, Nolden-Koch M, Schwarz M. | title=Rolipram reduces excitotoxic neuronal damage | journal=Neuroreport | year=2001 | pages=1507–11 | volume=12 | issue=7 | pmid=11388438 | doi=10.1097/00001756-200105250-00041}}</ref><ref name="PDEIs-Neuroprotection-Chen">{{cite journal | author=Chen RW, Williams AJ, Liao Z, Yao C, Tortella FC, Dave JR. | title=Broad spectrum neuroprotection profile of phosphodiesterase inhibitors as related to modulation of cell-cycle elements and caspase-3 activation | journal=Neuroscience Letters | year=2007 | pages=165–9 | volume=418 | issue=2 | pmid=17398001 | doi=10.1016/j.neulet.2007.03.033}}</ref>
	Rolipram shows promise in ameliorating ],<ref name='PNAS 2009-9-14'>{{cite journal|title=Reversal of long-term dendritic spine alterations in Alzheimer disease models|journal=Proceedings of the National Academy of Sciences of the United States | date=September 14, 2009 | first=Donna L|last= Smith|coauthors=Pozueta J, Gong B, Arancio O, Shelanski M | volume=106 | issue=39 | pages=16877–16882 | pmid= 19805389 | doi = 10.1073/pnas.0908706106 | url=http://www.pnas.org/content/106/39/16877.full|format=|accessdate=2009-11-13|pmc=423273 }}</ref> ] <ref name='U. S. ARMY MEDICAL RESEARCH 2005 1-1'>{{cite web|url=http://handle.dtic.mil/100.2/ADA434051 |title=Oxidative Damage in Parkinson's Disease |accessdate=2009-11-13 |last=MF |first=Beal |coauthors=Cleren C, Calingasan NY, Yang L, Klivenyi P, Lorenzl S |year=2005 |publisher=U.S. Army Medical Research and Materiel CommandFort Detrick, Maryland 21702-5012 }}</ref> and also in the regeneration of severed spinal cord axonal bodies.<ref name='NCBI PUB/MED.GOV Jun. 8, 2004'> {{cite journal|title=The Phosphodiesterase Inhibitor Rolipram Delivered after a Spinal Cord Lesion Promotes Axonal Regeneration and Functional Recovery|journal=Proceedings of the National Academy of Sciences of the United States|date=Jun. 8, 2004|first=E|last=Nikulina|coauthors=Tidwell JL, Dai HN, Bregman BS, Filbin MT, Goodman CS|volume=101|issue=23|pages=8786–8790|pmid=15173585 |url=http://www.ncbi.nlm.nih.gov/pubmed/15173585|format=|accessdate=2009-11-13|doi=10.1073/pnas.0402595101|pmc=423273 }}</ref>
			Rolipram has several activities that make it a continuing focus for research. The etiology of many ] involves misfolded and clumped proteins which accumulate in the brain. Cells have a mechanism to dispose of such proteins called the ]. However, in ] and some other conditions the activity of these proteasomes is impaired leading to a buildup of toxic aggregates. Research in mice suggests that rolipram has the ability to ramp up the activity of proteasomes and reduce the burden of these aggregates. Preliminary evidence suggests that this can improve spatial memory in mice engineered to have aggregate build-up.<ref name="Myeku 46-53">{{cite journal | vauthors = Myeku N, Clelland CL, Emrani S, Kukushkin NV, Yu WH, Goldberg AL, Duff KE | title = Tau-driven 26S proteasome impairment and cognitive dysfunction can be prevented early in disease by activating cAMP-PKA signaling | journal = Nature Medicine | volume = 22 | issue = 1 | pages = 46–53 | date = January 2016 | pmid = 26692334 | pmc = 4787271 | doi = 10.1038/nm.4011 }}</ref> Rolipram continues to be used in research as a well-characterized PDE4 inhibitor.<ref name=McKenna/>{{rp|669}} It has been used in studies to understand whether PDE4 inhibition could be useful in ],<ref>{{cite journal | vauthors = Kumar N, Goldminz AM, Kim N, Gottlieb AB | title = Phosphodiesterase 4-targeted treatments for autoimmune diseases | journal = BMC Medicine | volume = 11 | issue = 1 | pages = 96 | date = April 2013 | pmid = 23557064 | pmc = 3616808 | doi = 10.1186/1741-7015-11-96 | doi-access = free }}</ref> Alzheimer's disease,<ref>{{cite journal | vauthors = García-Osta A, Cuadrado-Tejedor M, García-Barroso C, Oyarzábal J, Franco R | title = Phosphodiesterases as therapeutic targets for Alzheimer's disease | journal = ACS Chemical Neuroscience | volume = 3 | issue = 11 | pages = 832–844 | date = November 2012 | pmid = 23173065 | pmc = 3503343 | doi = 10.1021/cn3000907 }}</ref> cognitive enhancement,<ref>{{cite journal | vauthors = Normann C, Berger M | title = Neuroenhancement: status quo and perspectives | journal = European Archives of Psychiatry and Clinical Neuroscience | volume = 258 | issue = Suppl 5 | pages = 110–114 | date = November 2008 | pmid = 18985306 | doi = 10.1007/s00406-008-5022-2 | s2cid = 9733191 }}</ref> spinal cord injury,<ref>{{cite journal | vauthors = Hannila SS, Filbin MT | title = The role of cyclic AMP signaling in promoting axonal regeneration after spinal cord injury | journal = Experimental Neurology | volume = 209 | issue = 2 | pages = 321–332 | date = February 2008 | pmid = 17720160 | pmc = 2692909 | doi = 10.1016/j.expneurol.2007.06.020 }}</ref> and respiratory diseases like ] and ].<ref>{{cite journal | vauthors = Huang Z, Mancini JA | title = Phosphodiesterase 4 inhibitors for the treatment of asthma and COPD | journal = Current Medicinal Chemistry | volume = 13 | issue = 27 | pages = 3253–3262 | year = 2006 | pmid = 17168849 | doi = 10.2174/092986706778773040 }}</ref>
	==See also==
	*]s
	==References==		== See also ==
			*]
⚫	{{Reflist}}
			== References ==
		⚫	{{Reflist|33em}}
	{{Phosphodiesterase inhibitors}}		{{Phosphodiesterase inhibitors}}
	]		]
⚫	]
	]		]
		⚫	]
			]
	]
			]
	]