ロリプラム
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IUPAC命名法による物質名 | |
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臨床データ | |
法的規制 |
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薬物動態データ | |
半減期 | 1–3 h |
識別 | |
CAS番号 | 61413-54-5 ![]() 87714-57-6 [要出典] |
ATCコード | none |
PubChem | CID: 5092 |
DrugBank | DB04149 ![]() |
ChemSpider | 4913 ![]() |
UNII | K676NL63N7 ![]() |
ChEBI | CHEBI:104872 ![]() |
ChEMBL | CHEMBL63 ![]() |
化学的データ | |
化学式 | C16H21NO3 |
分子量 | 275.347 g/mol |
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テンプレートを表示 |
ロリプラム(Rolipram)は、選択的ホスホジエステラーゼ阻害薬である。ホスホジエステラーゼ-4、特にPDE-IVBを阻害する[1]。多くのPDE阻害剤と同様に、ロリプラムは抗炎症薬である[2]。また、抗うつ薬としての用途が研究されている[1][3][4]。また、抗炎症[5]、免疫抑制[5]、抗腫瘍活性[6][7]も持ち、様々な硬化症の治療も提案されている[8]。近年の研究では、抗精神病薬の効果も持つことが示されている[9][10]。動物実験で示されたその他の効果は次の通りである。
動物実験により、アルツハイマー病[16]やパーキンソン病[17]の症状改善や脊椎軸索の再生[18]の可能性も示されている。
ロリプラムには、嘔吐やその他の望ましくない効果もある[19]。この点では、ネズミで嘔吐を起こさない程度の服用量でロリプラムの3倍から10倍の記憶改善効果を持つ別のPDE4阻害剤であるGEBR-7bよりも好ましくない[20]。
関連項目
出典
- ^ a b Zhu, J; Mix, E; Winblad, B (2001 Winter). “The antidepressant and antiinflammatory effects of rolipram in the central nervous system.”. CNS drug reviews 7 (4): 387–98. PMID 11830756.
- ^ Griswold DE, Webb EF, Breton J, White JR, Marshall PJ, Torphy TJ. (1993). “Effect of selective phosphodiesterase type IV inhibitor, rolipram, on fluid and cellular phases of inflammatory response”. Inflammation 17 (3): 333–44. doi:10.1007/BF00918994. PMID 7687237.
- ^ 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. (1988). “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”. Eur Arch Psychiatry Neurol Sci 238 (1): 2–6. doi:10.1007/BF00381071. PMID 3063534.
- ^ Wachtel H. (1983). “Potential antidepressant activity of rolipram and other selective cyclic adenosine 3',5'-monophosphate phosphodiesterase inhibitors”. Neuropharmacology 22 (3): 267–72. doi:10.1016/0028-3908(83)90239-3. PMID 6302550.
- ^ a b Sommer, N; Löschmann, PA; Northoff, GH; Weller, M; Steinbrecher, A; Steinbach, JP; Lichtenfels, R; Meyermann, R; Riethmüller, A; Fontana, A (1995 Mar). “The antidepressant rolipram suppresses cytokine production and prevents autoimmune encephalomyelitis.”. Nature medicine 1 (3): 244–8. PMID 7585041.
- ^ Chen, TC; Wadsten, P; Su, S; Rawlinson, N; Hofman, FM; Hill, CK; Schönthal, AH (2002 May-Jun). “The type IV phosphodiesterase inhibitor rolipram induces expression of the cell cycle inhibitors p21(Cip1) and p27(Kip1), resulting in growth inhibition, increased differentiation, and subsequent apoptosis of malignant A-172 glioma cells.”. Cancer biology & therapy 1 (3): 268–76. PMID 12432276.
- ^ Semmler, J; Wachtel, H; Endres, S (1993 Apr). “The specific type IV phosphodiesterase inhibitor rolipram suppresses tumor necrosis factor-alpha production by human mononuclear cells.”. International journal of immunopharmacology 15 (3): 409–13. PMID 8505151.
- ^ Mendes, E; Wadsten, P; Su, S; Rawlinson, N; Hofman, FM; Hill, CK; Schönthal, AH (1975 Nov). “Immunological studies on bronchial secretion. I. Antigenic relationship between bronchial secretion and serum: bronchial secretion constituents detected in human sera.”. Acta allergologica 30 (5): 259–66. PMID 12432276.
- ^ Maxwell CR, Kanes SJ, Abel T, Siegel SJ. (2004). “Phosphodiesterase inhibitors: a novel mechanism for receptor-independent antipsychotic medications”. Neuroscience 129 (1): 101–7. doi:10.1016/j.neuroscience.2004.07.038. PMID 15489033.
- ^ Kanes SJ, Tokarczyk J, Siegel SJ, Bilker W, Abel T, Kelly MP. (2006). “Rolipram: A specific phosphodiesterase 4 inhibitor with potential antipsychotic activity”. Neuroscience 144 (1): 239–46. doi:10.1016/j.neuroscience.2006.09.026. PMC 3313447. PMID 17081698. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3313447/.
- ^ Barad M, Bourtchouladze R, Winder DG, Golan H, Kandel E. (1998). “Rolipram, a type IV-specific phosphodiesterase inhibitor, facilitates the establishment of long-lasting long-term potentiation and improves memory”. Proceedings of the National Academy of Sciences of the United States of America 95 (25): 15020–5. doi:10.1073/pnas.95.25.15020. PMC 24568. PMID 9844008. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC24568/.
- ^ Lelkes Z, Alföldi P, Erdos A, Benedek G. (1998). “Rolipram, an antidepressant that increases the availability of cAMP, transiently enhances wakefulness in rats”. Pharmacology, Biochemistry and Behaviour 60 (4): 835–9. doi:10.1016/S0091-3057(98)00038-0. PMID 9700966.
- ^ Block F, Schmidt W, Nolden-Koch M, Schwarz M. (2001). “Rolipram reduces excitotoxic neuronal damage”. Neuroreport 12 (7): 1507–11. doi:10.1097/00001756-200105250-00041. PMID 11388438.
- ^ Chen RW, Williams AJ, Liao Z, Yao C, Tortella FC, Dave JR. (2007). “Broad spectrum neuroprotection profile of phosphodiesterase inhibitors as related to modulation of cell-cycle elements and caspase-3 activation”. Neuroscience Letters 418 (2): 165–9. doi:10.1016/j.neulet.2007.03.033. PMID 17398001.
- ^ Nikulina, Elena; J. Lille Tidwell, Hai Ning Dai, Barbara S. Bregman, and Marie T. Filbin (published ahead of print June 1, 2004). “The phosphodiesterase inhibitor rolipram delivered after a spinal cord lesion promotes axonal regeneration and functional recovery”. Proceedings of the National Academy of Sciences 101 (23): 8786. doi:10.1073/pnas.0402595101. http://www.pnas.org/content/101/23/8786.full 2012年10月13日閲覧。.
- ^ Smith, Donna L; Pozueta J, Gong B, Arancio O, Shelanski M (September 14, 2009). “Reversal of long-term dendritic spine alterations in Alzheimer disease models”. Proceedings of the National Academy of Sciences of the United States 106 (39): 16877–16882. doi:10.1073/pnas.0908706106. PMC 2743726. PMID 19805389. http://www.pnas.org/content/106/39/16877.full 2009年11月13日閲覧。.
- ^ MF, Beal; Cleren C, Calingasan NY, Yang L, Klivenyi P, Lorenzl S (2005年). “Oxidative Damage in Parkinson's Disease”. U.S. Army Medical Research and Materiel CommandFort Detrick, Maryland 21702-5012. 2009年11月13日閲覧。
- ^ Nikulina, E. (June 8, 2004). “The Phosphodiesterase Inhibitor Rolipram Delivered after a Spinal Cord Lesion Promotes Axonal Regeneration and Functional Recovery”. Proceedings of the National Academy of Sciences of the United States 101 (23): 8786. doi:10.1073/pnas.0402595101. JSTOR 3372336.
- ^ “Emetic, central nervous system, and pulmonary activities of rolipram in the dog.”. 2013年7月2日閲覧。
- ^ “GEBR-7b, a novel PDE4D selective inhibitor that improves memory in rodents at non-emetic doses.”. 2013年7月2日閲覧。