GEBR-7b, a novel PDE4D selective inhibitor that improves memory in rodents at non-emetic doses

O. Bruno; E. Fedele; J. Prickaerts; L. A. Parker; E. Canepa; Chiara Brullo; A. Cavallero; Elena Gardella; A. Balbi; C. Domenicotti; E. Bollen; Hieronymus J. M. Gijselaers; T. Vanmierlo; K. Erb; C. L. Limebeer; F. Argellati; U. M. Marinari; Maria Adelaide Pronzato; R. Ricciarelli

doi:10.1111/j.1476-5381.2011.01524.x

GEBR-7b, a novel PDE4D selective inhibitor that improves memory in rodents at non-emetic doses

O. Bruno, E. Fedele, J. Prickaerts, L. A. Parker, E. Canepa, Chiara Brullo, A. Cavallero, Elena Gardella, A. Balbi, C. Domenicotti, E. Bollen, Hieronymus J. M. Gijselaers, T. Vanmierlo, K. Erb, C. L. Limebeer, F. Argellati, U. M. Marinari, Maria Adelaide Pronzato, R. Ricciarelli^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND AND PURPOSE Strategies designed to enhance cerebral cAMP have been proposed as symptomatic treatments to counteract cognitive deficits. However, pharmacological therapies aimed at reducing PDE4, the main class of cAMP catabolizing enzymes in the brain, produce severe emetic side effects. We have recently synthesized a 3-cyclopentyloxy-4-methoxybenzaldehyde derivative, structurally related to rolipram, and endowed with selective PDE4D inhibitory activity. The aim of the present study was to investigate the effect of the new drug, namely GEBR-7b, on memory performance, nausea, hippocampal cAMP and amyloid-beta (A beta) levels.

Original language	English
Pages (from-to)	2054-2063
Journal	British Journal of Pharmacology
Volume	164
Issue number	8
DOIs	https://doi.org/10.1111/j.1476-5381.2011.01524.x
Publication status	Published - Dec 2011

Keywords

PDE4 inhibitor
memory
phosphodiesterase
cyclic AMP
rolipram
emesis

Access to Document

10.1111/j.1476-5381.2011.01524.x

Cite this

Bruno, O., Fedele, E., Prickaerts, J., Parker, L. A., Canepa, E., Brullo, C., Cavallero, A., Gardella, E., Balbi, A., Domenicotti, C., Bollen, E., Gijselaers, H. J. M., Vanmierlo, T., Erb, K., Limebeer, C. L., Argellati, F., Marinari, U. M., Pronzato, M. A., & Ricciarelli, R. (2011). GEBR-7b, a novel PDE4D selective inhibitor that improves memory in rodents at non-emetic doses. British Journal of Pharmacology, 164(8), 2054-2063. https://doi.org/10.1111/j.1476-5381.2011.01524.x

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title = "GEBR-7b, a novel PDE4D selective inhibitor that improves memory in rodents at non-emetic doses",

abstract = "BACKGROUND AND PURPOSE Strategies designed to enhance cerebral cAMP have been proposed as symptomatic treatments to counteract cognitive deficits. However, pharmacological therapies aimed at reducing PDE4, the main class of cAMP catabolizing enzymes in the brain, produce severe emetic side effects. We have recently synthesized a 3-cyclopentyloxy-4-methoxybenzaldehyde derivative, structurally related to rolipram, and endowed with selective PDE4D inhibitory activity. The aim of the present study was to investigate the effect of the new drug, namely GEBR-7b, on memory performance, nausea, hippocampal cAMP and amyloid-beta (A beta) levels.",

keywords = "PDE4 inhibitor, memory, phosphodiesterase, cyclic AMP, rolipram, emesis",

author = "O. Bruno and E. Fedele and J. Prickaerts and Parker, {L. A.} and E. Canepa and Chiara Brullo and A. Cavallero and Elena Gardella and A. Balbi and C. Domenicotti and E. Bollen and Gijselaers, {Hieronymus J. M.} and T. Vanmierlo and K. Erb and Limebeer, {C. L.} and F. Argellati and Marinari, {U. M.} and Pronzato, {Maria Adelaide} and R. Ricciarelli",

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Bruno, O, Fedele, E, Prickaerts, J, Parker, LA, Canepa, E, Brullo, C, Cavallero, A, Gardella, E, Balbi, A, Domenicotti, C, Bollen, E, Gijselaers, HJM, Vanmierlo, T, Erb, K, Limebeer, CL, Argellati, F, Marinari, UM, Pronzato, MA & Ricciarelli, R 2011, 'GEBR-7b, a novel PDE4D selective inhibitor that improves memory in rodents at non-emetic doses', British Journal of Pharmacology, vol. 164, no. 8, pp. 2054-2063. https://doi.org/10.1111/j.1476-5381.2011.01524.x

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T1 - GEBR-7b, a novel PDE4D selective inhibitor that improves memory in rodents at non-emetic doses

AU - Bruno, O.

AU - Fedele, E.

AU - Prickaerts, J.

AU - Parker, L. A.

AU - Canepa, E.

AU - Brullo, Chiara

AU - Cavallero, A.

AU - Gardella, Elena

AU - Balbi, A.

AU - Domenicotti, C.

AU - Bollen, E.

AU - Gijselaers, Hieronymus J. M.

AU - Vanmierlo, T.

AU - Erb, K.

AU - Limebeer, C. L.

AU - Argellati, F.

AU - Marinari, U. M.

AU - Pronzato, Maria Adelaide

AU - Ricciarelli, R.

PY - 2011/12

Y1 - 2011/12

N2 - BACKGROUND AND PURPOSE Strategies designed to enhance cerebral cAMP have been proposed as symptomatic treatments to counteract cognitive deficits. However, pharmacological therapies aimed at reducing PDE4, the main class of cAMP catabolizing enzymes in the brain, produce severe emetic side effects. We have recently synthesized a 3-cyclopentyloxy-4-methoxybenzaldehyde derivative, structurally related to rolipram, and endowed with selective PDE4D inhibitory activity. The aim of the present study was to investigate the effect of the new drug, namely GEBR-7b, on memory performance, nausea, hippocampal cAMP and amyloid-beta (A beta) levels.

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KW - PDE4 inhibitor

KW - memory

KW - phosphodiesterase

KW - cyclic AMP

KW - rolipram

KW - emesis

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