Rolipram in Major Depressive Disorder: Results of a Double-Blind Comparative Study with Imipramine

Hebenstreit, G.; Fellerer, Katrin; Fichte, K; Fischer, Gabija; Geyer, Nathaniel R.; Meya, U.; Sastre-Y-Hernandez, M.; Schöny, W.; Schratzer, M.; Soukop, W.; Trampitsch, Ernst; Varosanec, S.; Zawada, Edward T.; Zöchling, Robert

doi:10.1055/s-2007-1014599

Cited by 141 publications

(78 citation statements)

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“…Rolipram was developed as an antidepressant and was used in clinical trials, but, because of side effects of emesis (nausea) in some patients, the trial was stopped (32)(33)(34). It has also been shown to have immunosuppressive and antiinflammatory effects (35).…”

Section: Discussionmentioning

confidence: 99%

The phosphodiesterase inhibitor rolipram delivered after a spinal cord lesion promotes axonal regeneration and functional recovery

Nikulina

Tidwell

Dai

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

310

270

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Although there is no spontaneous regeneration of mammalian spinal axons after injury, they can be enticed to grow if cAMP is elevated in the neuronal cell bodies before the spinal axons are cut. Prophylactic injection of cAMP, however, is useless as therapy for spinal injuries. We now show that the phosphodiesterase 4 (PDE4) inhibitor rolipram (which readily crosses the blood-brain barrier) overcomes inhibitors of regeneration in myelin in culture and promotes regeneration in vivo. Two weeks after a hemisection lesion at C3͞4, with embryonic spinal tissue implanted immediately at the lesion site, a 10-day delivery of rolipram results in considerable axon regrowth into the transplant and a significant improvement in motor function. Surprisingly, in rolipram-treated animals, there was also an attenuation of reactive gliosis. Hence, because rolipram promotes axon regeneration, attenuates the formation of the glial scar, and significantly enhances functional recovery, and because it is effective when delivered s.c., as well as post-injury, it is a strong candidate as a useful therapy subsequent to spinal cord injury.

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Section: Discussionmentioning

confidence: 99%

The phosphodiesterase inhibitor rolipram delivered after a spinal cord lesion promotes axonal regeneration and functional recovery

Nikulina

Tidwell

Dai

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

310

270

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“…In the 1980s and early 1990s, a number of open (Zeller et al 1984) and controlled clinical trials (Bertolino et al 1988;Bobon et al 1988;Fleischhacker et al 1992;Hebenstreit et al 1989) demonstrated that rolipram, a specific inhibitor of the high-affinity cAMP PDE4, may have antidepressant efficacy in depressed patients. In addition, there is evidence that rolipram may have a faster onset of response compared with the standard antidepressants.…”

Section: Strategies To Potentiate the Creb/bdnf/ Bcl-2 Cascade For Thmentioning

confidence: 99%

“…In addition, there is evidence that rolipram may have a faster onset of response compared with the standard antidepressants. In the clinical study by Horowski and Sastre-YHernandez (1985), a rapid antidepressant effect to rolipram was reported to occur within the first 12 hours to 10 days, and another study (Zeller et al 1984) reported an antidepressant effect only after 2-4 days of treatment; however, in a randomized, double-blind comparative trial of rolipram versus imipramine, Hebenstreit et al (1989) found that imipramine was more effective than rolipram, though both were beneficial. Further, after a controlled study, Scott et al (1991) concluded that amitriptyline was more effective than rolipram in the treatment of depressed inpatients.…”

Section: Strategies To Potentiate the Creb/bdnf/ Bcl-2 Cascade For Thmentioning

confidence: 99%

Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for Difficult-to-Treat depression

Manji

Quiróz

Sporn

et al. 2003

Biological Psychiatry

445

259

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“…It elicits a morphine-withdrawal-like behavioral syndrome characterized by head twitches, forepaw shaking, grooming and hypoactivity, which are related to a high level of cAMP (Wachtel 1982;Wachtel 1983). Rolipram also exhibits antidepressant-like effects in animal models and in patients with depressive disorders (O'Donnell and Frith 1999;Hebenstreit et al 1989;O'Donnell 1993).Recently, rolipram has been shown to reverse the impairment of either working memory or reference memory induced by the muscarinic receptor antagonist scopolamine (Egawa et al 1997;Imanishi et al 1997;Zhang and O'Donnell 2000). Furthermore, PDE4 has been shown to be involved in NMDA receptor-mediated signal transduction mechanisms.…”

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confidence: 99%

Inhibition of Cyclic AMP Phosphodiesterase (PDE4) Reverses Memory Deficits Associated with NMDA Receptor Antagonism

Zhang

Crissman

Dorairaj

et al. 2000

Neuropsychopharmacology

148

105

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, a selective inhibitor of type 4 cyclic AMP phosphodiesterase (PDE4), completely reversed the amnesic effects of MK-801 on working and reference memory (F[4,64] ϭ 11.10; p Ͻ .0001 and F[4,64] N-methyl-D-aspartate (NMDA) receptors are widely distributed in the brain; their density is highest in the hippocampal CA1 subregion (Monaghan and Cotman 1985; Monyeret al. 1994;Boyer et al. 1998). It has been shown that NMDA receptors in this area are very important in the regulation of synaptic plasticity and the process of learning and memory, especially long-term memory (Kesner and Dakis 1995;Morris et al. 1986;Nguyen and Kandel 1996;Kawabe et al. 1998). Meanwhile, NMDA elicits an increase in cAMP in the hippocampal CA1 area that is antagonized by the competitive antagonist DL-2-amino-5-phosphonovaleric acid (AP5) or removal of extracellular Ca 2 ϩ (Chetkovich et al. 1991). Antagonism of NMDA receptors not only blocks NMDA-induced increases in cAMP, but also impairs learning and memory (Morris et al. 1986;Nguyen and Kandel 1996;Kawabe et al. 1998;Chetkovich et al. 1991;Meehan 1996). These results indicate that cAMP is involved in the NMDA receptor antagonist-induced impairment of learning and memory.Rolipram, a selective inhibitor of type 4 cAMP-specific phosphodiesterase (PDE4), produces an increase in brain cAMP levels via the inhibition of its degradation Rolipram Antagonizes MK-801-Induced Memory Deficits 199 (Schneider 1984;Ilien et al. 1982). Behavioral studies show that rolipram inhibits locomotor activity and rearing induced by methaphetamine and produces biphasic effects on schedule-controlled behavior, increasing response rate at lower doses and decreasing response rate at higher doses (Iyo et al. 1995;O'Donnell and Frith 1999). It elicits a morphine-withdrawal-like behavioral syndrome characterized by head twitches, forepaw shaking, grooming and hypoactivity, which are related to a high level of cAMP (Wachtel 1982;Wachtel 1983). Rolipram also exhibits antidepressant-like effects in animal models and in patients with depressive disorders (O'Donnell and Frith 1999;Hebenstreit et al. 1989;O'Donnell 1993).Recently, rolipram has been shown to reverse the impairment of either working memory or reference memory induced by the muscarinic receptor antagonist scopolamine (Egawa et al. 1997;Imanishi et al. 1997;Zhang and O'Donnell 2000). Furthermore, PDE4 has been shown to be involved in NMDA receptor-mediated signal transduction mechanisms. Chronic treatment with rolipram up-regulates NMDA receptors in the rat hippocampus ; rolipram also attenuates the expression of the heat shock protein HSP-70 induced by the NMDA receptor antagonist MK-801 (Hashimoto et al. 1997). Thus, although there is no direct evidence linking the effect of rolipram to NMDA receptors, the results described above suggest that rolipram will reverse the amnesic effect of the NMDA receptor antagonist MK-801. Such a finding would suggest an important role for PDE4 and cAMP in signal transduction mechanisms for NMDA receptors that are involved in ...

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Rolipram in Major Depressive Disorder: Results of a Double-Blind Comparative Study with Imipramine

Cited by 141 publications

References 0 publications

The phosphodiesterase inhibitor rolipram delivered after a spinal cord lesion promotes axonal regeneration and functional recovery

The phosphodiesterase inhibitor rolipram delivered after a spinal cord lesion promotes axonal regeneration and functional recovery

Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for Difficult-to-Treat depression

Inhibition of Cyclic AMP Phosphodiesterase (PDE4) Reverses Memory Deficits Associated with NMDA Receptor Antagonism

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