Rolipram

Structural formula
	1: 1 mixture of ( R ) -form (left) and ( S ) -form (right)
General
Non-proprietary name	Rolipram
other names	( RS ) -4- (3-Cyclopentyloxy-4-methoxyphenyl) pyrrolidin-2-one ( IUPAC ); (±) -4- (3-Cyclopentyloxy-4-methoxyphenyl) pyrrolidin-2-one; ZK 62711;
Molecular formula	C 16 H 21 NO 3
Brief description	white, crystalline, solid
External identifiers / databases
EC number	262-771-1
ECHA InfoCard	100.057.046
PubChem	5092
ChemSpider	4913
DrugBank	DB01954
Wikidata	Q410285
Drug information
Drug class	Phosphodiesterase inhibitors
Mechanism of action	PDE4 inhibition
properties
Molar mass	275.34 g mol −1
solubility	0.2 g l −1 in water, 7 g l −1 in ethanol, 7.3 g l −1 in DMSO
safety instructions
GHS labeling of hazardous substances Caution
H and P phrases	H: 315-319-335
	P: 261-305 + 351 + 338
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Rolipram is an experimental drug and was first described in the literature in 1979. It is an inhibitor of phosphodiesterase-4 and reduces the breakdown of the secondary messenger substance cAMP by intracellular phosphodiesterases. Rolipram is considered to be the archetype of phosphodiesterase 4 inhibitors.

Rolipram is a γ- lactam .

Effects in animal experiments

On the basis of animal experiments, among other things, the following effects are ascribed to rolipram:

antidepressant effects
antipsychotic effects
anti-inflammatory effects, especially in autoimmune diseases
positive effects on memory function
neuroprotective effects

Clinical effects

Rolipram was developed by Schering AG u. a. designed to treat depression and multiple sclerosis . However, it has not yet been approved as a medicinal product.

Most of the published information after use in humans is available for the indication of depression. However, clinical development in depression was discontinued because rolipram could not show any additional benefit compared to conventional antidepressants .

Development for multiple sclerosis was also discontinued.

Web links

Entries in the NIH study registry

Individual evidence

↑ ^a ^b ^c ^d Rolipram data sheet at Sigma-Aldrich , accessed on April 22, 2011 ( PDF ).

↑ H. Karppanen, P. Paakkari, AL Orma, I. Paakkari: Central hypotensive effects of imidazole acetic acid and rolipram (ZK 62711) in rats. In: Agents Actions. 9, 1979, pp. 84-86. PMID 223420 .

↑ H. Wachtel: Potential antidepressant activity of rolipram and other selective cyclic adenosine 3 ', 5'-monophosphate phosphodiesterase inhibitors. In: Neuropharmacology . 22, 1983, pp. 267-272, PMID 6302550 .

^ CR Maxwell, SJ Kanes, T. Abel, SJ Siegel: Phosphodiesterase inhibitors: a novel mechanism for receptor-independent antipsychotic medications. In: Neuroscience. 129, 2004, pp. 101-107, PMID 15489033 .

↑ SJ Kanes, J. Tokarczyk, SJ Siegel and others: Rolipram: a specific phosphodiesterase 4 inhibitor with potential antipsychotic activity. In: Neuroscience. 144, 2007, pp. 239-246, PMID 17081698 .

↑ DE Griswold, EF Webb, J. Breton et al .: Effect of selective phosphodiesterase type IV inhibitor, rolipram, on fluid and cellular phases of inflammatory response. In: Inflammation. 17, 1993, pp. 333-344, PMID 7687237 .

↑ N. Sommer, PA Löschmann, GH Northoff et al.: The antidepressant rolipram suppresses cytokine production and prevents autoimmune encephalomyelitis. In: Nat Med . 1, 1995, pp. 244-248, PMID 7585041 .

^ CT Randt, ME Judge, KA Bonnet, D. Quartermain: Brain cyclic AMP and memory in mice. In: Pharmacol Biochem Behav 17, 1982, pp. 677-680, PMID 6294676 .

↑ K. Rutten, J. Prickaerts, G. Schaenzle, H. Rosenbrock, A. Blokland: Sub-chronic rolipram treatment leads to a persistent improvement in long-term object memory in rats. In: Neurobiol Learn Mem. 90, 2008, pp. 569-575, PMID 18558503 .

↑ F. Block, W. Schmidt, M. Nolden-Koch, M. Schwarz: Rolipram reduces excitotoxic neuronal damage. In: Neuroreport. 12, 2001, pp. 1507-1511, PMID 11388438 .

Jump up ↑ E. Valera, FJ Sánchez-Martín, AV Ferrer-Montiel, A. Messeguer, JM Merino: NMDA-induced neuroprotection in hippocampal neurons is mediated through the protein kinase A and CREB (cAMP-response element-binding protein) pathway. In: Neurochem. Int. 53, 2008, pp. 148-154, PMID 18694792 .

^ E. Zeller, HJ Stief, B. Pflug, M. Sastre-y-Hernández: Results of a phase II study of the antidepressant effect of rolipram . In: Pharmacopsychiatry . 17, 1984, pp. 188-190. PMID 6393150 .

↑ GF Hebenstreit, K. Fellerer, K. Fichte et al .: Rolipram in major depressive disorder: results of a double-blind comparative study with imipramine. In: Pharmacopsychiatry. 22, 1989, pp. 156-160. PMID 2668980 .

↑ WW Fleischhacker, H. Hinterhuber, H. Bauer et al .: A multicenter double-blind study of three different doses of the new cAMP-phosphodiesterase inhibitor rolipram in patients with major depressive disorder. In: Neuropsychobiology. 26, 1992, pp. 59-64. PMID 1475038 .

↑ B. Bielekova, R. Orlowski, T. Howard et al .: Treatment of MS patients with selective PDE-4 inhibitor Rolipram inhibits Th1 / Th17 T cell responses, but fails to inhibit brain inflammatory activity . American Academy of Neurology 60th Annual Meeting; April 12-19, 2008; Chicago. In: Neurology. 70, 2008, p. S22.001.

[Sigma-1] Rolipram data sheet at Sigma-Aldrich , accessed on April 22, 2011 ( PDF ).

[2] H. Karppanen, P. Paakkari, AL Orma, I. Paakkari: Central hypotensive effects of imidazole acetic acid and rolipram (ZK 62711) in rats. In: Agents Actions. 9, 1979, pp. 84-86. PMID 223420 .

[3] H. Wachtel: Potential antidepressant activity of rolipram and other selective cyclic adenosine 3 ', 5'-monophosphate phosphodiesterase inhibitors. In: Neuropharmacology . 22, 1983, pp. 267-272, PMID 6302550 .

[4] CR Maxwell, SJ Kanes, T. Abel, SJ Siegel: Phosphodiesterase inhibitors: a novel mechanism for receptor-independent antipsychotic medications. In: Neuroscience. 129, 2004, pp. 101-107, PMID 15489033 .

[5] SJ Kanes, J. Tokarczyk, SJ Siegel and others: Rolipram: a specific phosphodiesterase 4 inhibitor with potential antipsychotic activity. In: Neuroscience. 144, 2007, pp. 239-246, PMID 17081698 .

[6] DE Griswold, EF Webb, J. Breton et al .: Effect of selective phosphodiesterase type IV inhibitor, rolipram, on fluid and cellular phases of inflammatory response. In: Inflammation. 17, 1993, pp. 333-344, PMID 7687237 .

[7] N. Sommer, PA Löschmann, GH Northoff et al.: The antidepressant rolipram suppresses cytokine production and prevents autoimmune encephalomyelitis. In: Nat Med . 1, 1995, pp. 244-248, PMID 7585041 .

[8] CT Randt, ME Judge, KA Bonnet, D. Quartermain: Brain cyclic AMP and memory in mice. In: Pharmacol Biochem Behav 17, 1982, pp. 677-680, PMID 6294676 .

[PMID18558503-9] K. Rutten, J. Prickaerts, G. Schaenzle, H. Rosenbrock, A. Blokland: Sub-chronic rolipram treatment leads to a persistent improvement in long-term object memory in rats. In: Neurobiol Learn Mem. 90, 2008, pp. 569-575, PMID 18558503 .

[10] F. Block, W. Schmidt, M. Nolden-Koch, M. Schwarz: Rolipram reduces excitotoxic neuronal damage. In: Neuroreport. 12, 2001, pp. 1507-1511, PMID 11388438 .

[PMID18694792-11] Jump up ↑ E. Valera, FJ Sánchez-Martín, AV Ferrer-Montiel, A. Messeguer, JM Merino: NMDA-induced neuroprotection in hippocampal neurons is mediated through the protein kinase A and CREB (cAMP-response element-binding protein) pathway. In: Neurochem. Int. 53, 2008, pp. 148-154, PMID 18694792 .

[12] E. Zeller, HJ Stief, B. Pflug, M. Sastre-y-Hernández: Results of a phase II study of the antidepressant effect of rolipram . In: Pharmacopsychiatry . 17, 1984, pp. 188-190. PMID 6393150 .

[13] GF Hebenstreit, K. Fellerer, K. Fichte et al .: Rolipram in major depressive disorder: results of a double-blind comparative study with imipramine. In: Pharmacopsychiatry. 22, 1989, pp. 156-160. PMID 2668980 .

[14] WW Fleischhacker, H. Hinterhuber, H. Bauer et al .: A multicenter double-blind study of three different doses of the new cAMP-phosphodiesterase inhibitor rolipram in patients with major depressive disorder. In: Neuropsychobiology. 26, 1992, pp. 59-64. PMID 1475038 .

[15] B. Bielekova, R. Orlowski, T. Howard et al .: Treatment of MS patients with selective PDE-4 inhibitor Rolipram inhibits Th1 / Th17 T cell responses, but fails to inhibit brain inflammatory activity . American Academy of Neurology 60th Annual Meeting; April 12-19, 2008; Chicago. In: Neurology. 70, 2008, p. S22.001.