| Revision as of 13:06, 6 December 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 456598123 of page Rolipram for the Chem/Drugbox validation project (updated: 'DrugBank'). |
Latest revision as of 18:38, 8 December 2023 edit Boghog (talk | contribs)Autopatrolled, Extended confirmed users, IP block exemptions, New page reviewers, Pending changes reviewers, Rollbackers, Template editors137,723 edits consistent citation formatting |
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{{Short description|Chemical compound}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}} |
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{{Drugbox |
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{{Drugbox |
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| Verifiedfields = changed |
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| Verifiedfields = changed |
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| Watchedfields = changed |
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| verifiedrevid = 407336426 |
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| verifiedrevid = 464383368 |
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| IUPAC_name = (''RS'')-4-(3-cyclopentyloxy-4-methoxy-phenyl)pyrrolidin-2-one |
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| IUPAC_name = (''RS'')-4-(3-cyclopentyloxy-4-methoxy-phenyl)pyrrolidin-2-one |
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| image = rolipram.svg |
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| image = Rolipram.svg |
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| width = 200px |
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| width = 200 |
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| imagename = 1 : 1 mixture (racemate) |
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| drug_name = Rolipram |
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<!--Clinical data--> |
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<!--Clinical data--> |
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| tradename = |
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| tradename = |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| pregnancy_US = <!-- A / B / C / D / X --> |
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| pregnancy_US = <!-- A / B / C / D / X --> |
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| pregnancy_category = |
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| pregnancy_category = |
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| legal_AU = <!-- Unscheduled / S2 / S4 / S8 --> |
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| legal_AU = <!-- Unscheduled / S2 / S4 / S8 --> |
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| legal_UK = <!-- GSL / P / POM / CD --> |
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| legal_UK = <!-- GSL / P / POM / CD --> |
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| legal_US = <!-- OTC / Rx-only --> |
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| legal_US = <!-- OTC / Rx-only --> |
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| legal_status = |
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| legal_status = Investigational |
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| routes_of_administration = |
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| routes_of_administration = |
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<!--Pharmacokinetic data--> |
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<!--Pharmacokinetic data--> |
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| 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> |
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| bioavailability = |
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| protein_bound = |
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| protein_bound = |
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| metabolism = ] via ], ], ] and ]<ref name = PK/> |
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| metabolism = |
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| elimination_half-life = 1-3 h |
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| elimination_half-life = 3 hours<ref name = PK/> |
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| excretion = |
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| excretion = Urine (80%)<ref name = PK/> |
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<!--Identifiers--> |
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<!--Identifiers--> |
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| IUPHAR_ligand = 5260 |
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| CASNo_Ref = {{cascite}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 61413-54-5 |
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| CAS_number = 61413-54-5 |
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| ATC_prefix = none |
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| ATC_prefix = none |
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| ATC_suffix = |
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| ATC_suffix = |
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| ATC_supplemental = |
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| ATC_supplemental = |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 4913 |
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| ChemSpiderID = 4913 |
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| ChEBI_Ref = {{ebicite|changed|EBI}} |
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| ChEBI_Ref = {{ebicite|correct|EBI}} |
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| ChEBI = 104872 |
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| ChEBI = 104872 |
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| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| 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) |
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| 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) |
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| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = HJORMJIFDVBMOB-UHFFFAOYSA-N |
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| StdInChIKey = HJORMJIFDVBMOB-UHFFFAOYSA-N |
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| PubChem = 5092 |
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| PubChem = 5092 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank_Ref = {{drugbankcite|changed|drugbank}} |
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| DrugBank = <!-- blanked - oldvalue: EXPT00228 --> |
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| DrugBank = DB04149 |
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| UNII_Ref = {{fdacite|changed|FDA}} |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = K676NL63N7 |
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| UNII = K676NL63N7 |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = 63 |
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| ChEMBL = 63 |
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| KEGG_Ref = {{keggcite|changed|kegg}} |
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| KEGG = D01783 |
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<!--Chemical data--> |
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<!--Chemical data--> |
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| C=16 | H=21 | N=1 | O=3 |
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| C=16 | H=21 | N=1 | O=3 |
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| smiles = COc1ccc(cc1OC1CCCC1)C1CNC(=O)C1 |
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| molecular_weight = 275.347 g/mol |
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}} |
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}} |
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'''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}} |
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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> |
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== See also == |
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*] |
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== References == |
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{{Reflist|33em}} |
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{{Phosphodiesterase inhibitors}} |
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