Calcium-independent phosphodiesterase inhibitors as putative antidepressants: [3-(bicycloalkyloxy)-4-methoxyphenyl-2-imidazolidinones

Saccomano, Nicholas A.; Vinick, Fredric J.; Koe, B. Kenneth; Nielsen, Jann A.; Whalen, W. M.; Meltz, Morgan; Phillips, Douglas; Thadieo, P. F.; Jung, Stanley; Chapin, Douglas C.; Lebel, Lorraine A.; Russo, Lorena L.; Helweg, David L.; Johnson, Jonathan L.; Ives, Jeffrey L.; Williams, Ian H.

doi:10.1021/jm00105a045

Cited by 45 publications

(18 citation statements)

References 4 publications

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“…It has been reported that the PDE4 inhibitor CP 76,593, even though more potent than rolipram for the inhibition of high-affinity [ 3 H]rolipram binding, is considerably less potent than rolipram for producing antidepressant-like effects on differential reinforcement of low response rate (DRL) behavior (O'Donnell, 1993). In addition, the potency order of a series of drugs for inhibition of high- (Saccomano et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

Antidepressant-Induced Increase in High-Affinity Rolipram Binding Sites in Rat Brain: Dependence on Noradrenergic and Serotonergic Function

Zhao¹,

Zhang²,

O'Donnell³

2003

J Pharmacol Exp Ther

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Section: Discussionmentioning

confidence: 99%

Antidepressant-Induced Increase in High-Affinity Rolipram Binding Sites in Rat Brain: Dependence on Noradrenergic and Serotonergic Function

Zhao¹,

Zhang²,

O'Donnell³

2003

J Pharmacol Exp Ther

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“…8 PDE4 hydrolyzes cyclic AMP formed by stimulation of beta adrenergic receptor-linked adenylyl cyclase in brain cortical slices. 9 Rolipram or other selective inhibitors of PDE4 have antidepressant activity in both preclinical 10 and clinical tests 11 and produces memory-enhancing effects in animal models. 12,13 Repeated treatment of animals with SNRIs may up-regulate PDE4.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of serotonin and norepinephrine reuptake and inhibition of phosphodiesterase by multi-target inhibitors as potential agents for depression

Cashman

Ghirmai

2009

Bioorganic & Medicinal Chemistry

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“…This has been confirmed using [ 3 H]-3-(cyclopentyloxy)-N-(3,5-dichloropyridin-4-yl)-4-methoxybenzamide (piclamilast), which binds with equal high affinity to the HARBS and LARBS (Zhao et al, 2003a). Although the LARBS is found in both the brain and peripheral tissues, the HARBS is found only in the brain; consistent with this, the HARBS and LARBS mediate distinct pharmacological effects (Saccomano et al, 1991;Barnette et al, 1996;Zhao et al, 2003b).…”

Section: Introductionmentioning

confidence: 61%

Effects of Repeated Treatment with Phosphodiesterase-4 Inhibitors on cAMP Signaling, Hippocampal Cell Proliferation, and Behavior in the Forced-Swim Test

Xiao¹,

O’Callaghan²,

O'Donnell³

2011

J Pharmacol Exp Ther

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The effects of repeated treatment with the phosphodiesterase-4 (PDE4) inhibitors rolipram, piclamilast, and 4-(2-(3-(cyclopentyloxy)-4-methoxyphenyl)-2-phenylethyl)pyridine (CDP840), which differ in their interactions with high-and low-affinity binding conformers of the enzyme, were contrasted to those of acute treatment on cAMP signaling, hippocampal cell proliferation, and immobility in the forced-swim test in rats. Repeated treatment with rolipram (1 and 3 mg/kg), piclamilast (0.3 and 1 mg/kg), or CDP840 (10 and 30 mg/kg) for 16 days increased cAMP and phosphorylation of cAMP response element binding protein (pCREB) in hippocampus and prefrontal cortex. In addition, repeated treatment with the PDE4 inhibitors increased proliferation and survival of newborn cells in the hippocampus and produced antidepressant-like effects on behavior, as evidenced by decreased immobility in the forced-swim test. Acute treatment with rolipram (3 mg/kg), piclamilast (1 mg/kg), or CDP840 (30 mg/kg) induced transient increases in cAMP and pCREB in hippocampus and prefrontal cortex, but the dose and time dependence of these effects did not parallel the behavioral effects. Compared with rolipram and piclamilast, repeated treatment with CDP840 exerted lesser effects on neural and behavioral measures, probably because of its weak interaction with the high-affinity binding conformer of PDE4. This suggests the relative importance of the high-affinity binding conformer in the mediation of the long-term effects of PDE4 inhibition on cAMP/pCREB signaling, hippocampal cell proliferation, and antidepressant-like effects on behavior.

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Calcium-independent phosphodiesterase inhibitors as putative antidepressants: [3-(bicycloalkyloxy)-4-methoxyphenyl-2-imidazolidinones

Cited by 45 publications

References 4 publications

Antidepressant-Induced Increase in High-Affinity Rolipram Binding Sites in Rat Brain: Dependence on Noradrenergic and Serotonergic Function

Antidepressant-Induced Increase in High-Affinity Rolipram Binding Sites in Rat Brain: Dependence on Noradrenergic and Serotonergic Function

Inhibition of serotonin and norepinephrine reuptake and inhibition of phosphodiesterase by multi-target inhibitors as potential agents for depression

Effects of Repeated Treatment with Phosphodiesterase-4 Inhibitors on cAMP Signaling, Hippocampal Cell Proliferation, and Behavior in the Forced-Swim Test

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