The PDE4 inhibitor roflumilast improves memory in rodents at non-emetic doses

Behavioural Brain Research

Volumn 303, Issue , 2016, Pages 26-33

  Vanmierlo, Tim ^a,b   Creemers, Pim ^a,d   Akkerman, Sven ^a   van Duinen, Marlies ^a   Sambeth, Anke ^a   De Vry, Jochen ^a   Uz, Tolga ^c   Blokland, Arjan ^a   Prickaerts, Jos ^a  

^a MAASTRICHT UNIVERSITY   (Netherlands)

^b HASSELT UNIVERSITY   (Belgium)

^c TAKEDA DEVELOPMENT CENTER AMERICAS   (United States)

^d Boston Scientific Corporation   (Netherlands)

Author keywords

CAMP; Cognition; Emesis; Memory; PDE4; PDE4 inhibition; Roflumilast; Rolipram

Indexed keywords

DONEPEZIL; ROFLUMILAST; ROLIPRAM; AMINOPYRIDINE DERIVATIVE; BENZAMIDE DERIVATIVE; CYCLOPROPANE DERIVATIVE; INDAN DERIVATIVE; NOOTROPIC AGENT; PHOSPHODIESTERASE IV INHIBITOR; PIPERIDINE DERIVATIVE; SCOPOLAMINE BROMIDE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; COMBINATION CHEMOTHERAPY; CONTROLLED STUDY; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG EFFICACY; DRUG POTENCY; DRUG POTENTIATION; EXPLORATORY BEHAVIOR; MALE; MEMORY DISORDER; MOUSE; NONHUMAN; PRIORITY JOURNAL; SPATIAL MEMORY; TASK PERFORMANCE; VOMITING; Y-MAZE TEST; ANIMAL; C57BL MOUSE; CHEMICALLY INDUCED; DRUG EFFECTS; MEMORY; RECOGNITION; WISTAR RAT;

AMINOPYRIDINES; ANIMALS; BENZAMIDES; CYCLOPROPANES; INDANS; MALE; MEMORY; MICE; MICE, INBRED C57BL; NOOTROPIC AGENTS; PHOSPHODIESTERASE 4 INHIBITORS; PIPERIDINES; RATS, WISTAR; RECOGNITION (PSYCHOLOGY); ROLIPRAM; SCOPOLAMINE HYDROBROMIDE; SPATIAL MEMORY; VOMITING;

EID: 84961322053     PISSN: 01664328     EISSN: 18727549     Source Type: Journal    
DOI: 10.1016/j.bbr.2016.01.031     Document Type: Article

References (62)

1. Silvestre J.S., Fernández A.G., Palacios J.M. Preliminary evidence for an involvement of the cholinergic system in the sedative effects of rolipram in rats. Pharmacol. Biochem. Behav. 1999, 64:1-5.
2. Bailey C.H., Bartsch D., Kandel E.R. Toward a molecular definition of long-term memory storage. Proc. Nat. Acad. Sci. U. S. A. 1996, 93:13445.
3. Barad M., Bourtchouladze R., Winder D.G., Golan H., Rolipram K.E. A type IV-specific phosphodiesterase inhibitor, facilitates the establishment of long-lasting long-term potentiation and improves memory. Proc. Nat. Acad. Sci. U. S. A. 1998, 95:15020.
4. Frey U., Huang Y., Kandel E. Effects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons. Science 1993, 260:1661-1664.
5. Li Y.F., Cheng Y.F., Huang Y., Conti M., Wilson S.P., O'Donnell J.M., et al. Phosphodiesterase-4D knock-out and RNA interference-mediated knock-down enhance memory and increase hippocampal neurogenesis via increased cAMP signaling. J. Neurosci. 2011, 31:172-183.
6. Zhang H.T. Cyclic AMP-specific phosphodiesterase-4 as a target for the development of antidepressant drugs. Curr. Pharm. Des. 2009, 15:1688-1698.
7. Dal Piaz V., Giovannoni M.P. Phosphodiesterase 4 inhibitors, structurally unrelated to rolipram, as promising agents for the treatment of asthma and other pathologies. Eur. J. Med. Chem. 2000, 35:463-480.
8. Martinez A., Gil C. cAMP-specific phosphodiesterase inhibitors: promising drugs for inflammatory and neurological diseases. Expert Opin. Ther. Patents 2014, 24:1311-1321.
9. Spina D. PDE4 inhibitors: current status. Br. J. Pharmacol. 2008, 155:308-315.
10. Burgin A.B., Magnusson O.T., Singh J., Witte P., Staker B.L., Bjornsson J.M., et al. Design of phosphodiesterase 4D (PDE4D) allosteric modulators for enhancing cognition with improved safety. Nat. Biotechnol. 2009, 28:63-70.
11. Reneerkens O.A.H., Rutten K., Steinbusch H.W.M., Blokland A., Prickaerts J. Selective phosphodiesterase inhibitors: a promising target for cognition enhancement. Psychopharmacology 2009, 202:419-443.
12. Braun N.N., Reutiman T.J., Lee S., Folsom T.D., Fatemi S.H. Expression of phosphodiesterase 4 is altered in the brains of subjects with autism. Neuroreport 2007, 18:1841-1844.
13. Ugarte A., Gil-Bea F., Garcia-Barroso C., Cedazo-Minguez A., Ramirez M.J., Franco R., et al. Decreased levels of cGMP in CSF are associated with cognitive decline and amyloid pathology in Alzheimer's disease. Neuropathol. Appl. Neurobiol. 2015, 41:471-482.
14. de Lima M.N., Presti-Torres J., Garcia V.A., Guimaraes M.R., Scalco F.S., Roesler R., et al. Amelioration of recognition memory impairment associated with iron loading or aging by the type 4-specific phosphodiesterase inhibitor rolipram in rats. Neuropharmacology 2008, 55:788-792.
15. McLachlan C.S., Chen M.L., Lynex C.N., Goh D.L., Brenner S., Tay S.K. Changes in PDE4D isoforms in the hippocampus of a patient with advanced Alzheimer disease. Arch. Neurol. 2007, 64:456-457.
16. Rutten K., Prickaerts J., Blokland A. Rolipram reverses scopolamine-induced and time-dependent memory deficits in object recognition by different mechanisms of action. Neurobiol. Learn. Mem. 2006, 85:132-138.
17. Hansen R.T., Zhang H.T. Phosphodiesterase-4 modulation as a potential therapeutic for cognitive loss in pathological and non-pathological aging: possibilities and pitfalls. Curr. Pharm. Des. 2015, 21:291-302.
18. Heckman P.R., Blokland A., Ramaekers J., Prickaerts J. PDE and cognitive processing: beyond the memory domain. Neurobiol. Learn. Mem. 2015, 119:108-122.
19. Richter W., Menniti F.S., Zhang H.T., Conti M. PDE4 as a target for cognition enhancement. Expert Opin. Ther. Targets 2013, 17:1011-1027.
20. Bach M.E., Barad M., Son H., Zhuo M., Lu Y.F., Shih R., et al. Age-related defects in spatial memory are correlated with defects in the late phase of hippocampal long-term potentiation in vitro and are attenuated by drugs that enhance the cAMP signaling pathway. Proc. Natl. Acad. Sci. U. S. A. 1999, 96:5280-5285.
21. Gong B., Vitolo O.V., Trinchese F., Liu S., Shelanski M., Arancio O. Persistent improvement in synaptic and cognitive functions in an Alzheimer mouse model after rolipram treatment. J. Clin. Investig. 2004, 114:1624-1634.
22. Rutten K., Basile J.L., Prickaerts J., Blokland A., Vivian J.A. Selective PDE inhibitors rolipram and sildenafil improve object retrieval performance in adult cynomolgus macaques. Psychopharmacology (Berl.) 2008, 196:643-648.
23. Sutcliffe J.S., Beaumont V., Watson J.M., Chew C.S., Beconi M., Hutcheson D.M., et al. Efficacy of selective PDE4D negative allosteric modulators in the object retrieval task in female cynomolgus monkeys (Macaca fascicularis). PLoS One 2014, 9:e102449.
24. Gallant M., Aspiotis R., Day S., Dias R., Dube D., Dube L., et al. Discovery of MK-0952, a selective PDE4 inhibitor for the treatment of long-term memory loss and mild cognitive impairment. Bioorg. Med. Chem. Lett. 2010, 20:6387-6393.
25. Girod V. Nausea and emesis models for the safety evaluation of PDE4 inhibitors. J. Pharmacol. Toxicol. Methods 2010, 62:e13-e14.
26. Hebenstreit G., Fellerer K., Fichte K., Fischer G. Rolipram in major depressive disorder: results of a double-blind comparative study with imipramine. Pharmacopsychiatry 1989, 22(4):156-160.
27. M. Puhan, Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease. The Cochrane database of systematic reviews. 2011: ED000028.
28. Rabe K.F., Bateman E.D., O'Donnell D., Witte S., Bethke T.D. Roflumilast-an oral anti-inflammatory treatment for chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 2005, 366:563-571.
29. Chong J., Poole P., Leung B., Black P.N. Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease. Cochrane Database Syst. Rev. 2011, 5.
30. Izquierdo J., Aparicio J. Roflumilast for COPD. Drugs Today (Barcelona, Spain: 1998) 2010, 46:823.
31. Claveau D., Chen S.L., O'Keefe S., Zaller D.M., Styhler A., Liu S., et al. Preferential inhibition of T helper 1, but not T helper 2, cytokines in vitro by L-826,141 [4-[2-(3,4-bisdifluromethoxyphenyl)-2-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-phenyl]-ethyl]3-methylpyridine-1-oxide], a potent and selective phosphodiesterase 4 inhibitor. J. Pharmacol. Exp. Ther. 2004, 310:752-760.
32. Robichaud A., Savoie C., Stamatiou P., Lachance N., Jolicoeur P., Rasori R., et al. Assessing the emetic potential of PDE4 inhibitors in rats. Br. J. Pharmacol. 2002, 135:113-118.
33. Robichaud A., Stamatiou P.B., Jin S.L.C., Lachance N., MacDonald D., Laliberté F., et al. Deletion of phosphodiesterase 4D in mice shortens alpha~ 2-adrenoceptor-mediated anesthesia, a behavioral correlate of emesis. J. Clin. Invest. 2002, 110:1045-1052.
34. Gurney M.E., D'Amato E.C., Burgin A.B. Phosphodiesterase-4 (PDE4) molecular pharmacology and Alzheimer's disease. Neurother.: J. Am. Soc. Exp. Neurother. 2015, 12:49-56.
35. Bruno O., Fedele E., Prickaerts J., Parker L., Canepa E., Brullo C., et al. GEBR-7b, a novel PDE4D selective inhibitor that improves memory in rodents at non-emetic doses. Br. J. Pharmacol. 2011, 164(8):2054-2063.
36. Ricciarelli R., Fedele E. Phosphodiesterase 4D: an enzyme to remember. Br. J. Pharmacol. 2015, 172:4785-4789.
37. Rutten K., Van Donkelaar E.L., Ferrington L., Blokland A., Bollen E., Steinbusch H.W., et al. Phosphodiesterase inhibitors enhance object memory independent of cerebral blood flow and glucose utilization in rats. Neuropsychopharmacology 2009, 34:1914-1925.
38. Ennaceur A., Delacour J. A new one-trial test for neurobiological studies of memory in rats. 1: behavioral data. Behav. Brain Res. 1988, 31:47-59.
39. Loveman E., Green C., Kirby J., Takeda A., Picot J., Payne E., et al. The Clinical and Cost-effectiveness of Donepezil, Rivastigmine Galantamine and Memantine for Alzheimer's Disease 2006, Gray Publishing.
40. Rutten K., Prickaerts J., Hendrix M., van der Staay F.J., Sik A., Blokland A. Time-dependent involvement of cAMP and cGMP in consolidation of object memory: studies using selective phosphodiesterase type 2, 4 and 5 inhibitors. Eur. J. Pharmacol. 2007, 558:107-112.
41. Prickaerts J., van Goethem N.P., Chesworth R., Shapiro G., Boess F.G., Methfessel C., et al. EVP-6124, a novel and selective alpha7 nicotinic acetylcholine receptor partial agonist, improves memory performance by potentiating the acetylcholine response of alpha7 nicotinic acetylcholine receptors. Neuropharmacology 2012, 62:1099-1110.
42. Vanmierlo T., Rutten K., Dederen J., Bloks V.W., van Vark-van der Zee L.C., Kuipers F., et al. Liver X receptor activation restores memory in aged AD mice without reducing amyloid. Neurobiol. Aging 2011, 32:1262-1272.
43. Akkerman S., Blokland A., Reneerkens O., van Goethem N.P., Bollen E., Gijselaers H.J., et al. Object recognition testing: methodological considerations on exploration and discrimination measures. Behav. Brain Res. 2012, 232:335-347.
44. Dellu F., Contarino A., Simon H., Koob G.F., Gold L.H. Genetic differences in response to novelty and spatial memory using a two-trial recognition task in mice. Neurobiol. Learn. Mem. 2000, 73:31-48.
45. Sierksma A.S., Prickaerts J., Chouliaras L., Rostamian S., Delbroek L., Rutten B.P., et al. Behavioral and neurobiological effects of prenatal stress exposure in male and female APPswe/PS1dE9 mice. Neurobiol. Aging 2013, 34:319-337.
46. Bruno O., Fedele E., Prickaerts J., Parker L.A., Canepa E., Brullo C., et al. GEBR-7b, a novel PDE4D selective inhibitor that improves memory in rodents at non-emetic doses. Br. J. Pharmacol. 2011, 164:2054-2063.
47. Jabaris S.G., Sumathy H., Kumar R.S., Narayanan S., Thanikachalam S., Babu C.S. Effects of rolipram and roflumilast, phosphodiesterase-4 inhibitors, on hypertension-induced defects in memory function in rats. Eur. J. Pharmacol. 2015, 746:138-147.
48. Peters M., Bletsch M., Stanley J., Wheeler D., Scott R., Tully T. The PDE4 inhibitor HT-0712 improves hippocampus-dependent memory in aged mice. Neuropsychopharmacology 2014, 39:2938-2948.
49. Hatzelmann A., Morcillo E.J., Lungarella G., Adnot S., Sanjar S., Beume R., et al. The preclinical pharmacology of roflumilast-a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease. Pulm. Pharmacol. Ther. 2010, 23:235-256.
50. J. Birks, L. Flicker, Donepezil for mild cognitive impairment. The Cochrane database of systematic reviews. 2006:CD006104.
51. Hitchcock S.A., Pennington L.D. Structure-brain exposure relationships. J. Med. Chem. 2006, 49:7559-7583.
52. Li Y.F., Cheng Y.F., Huang Y., Conti M., Wilson S.P., O'Donnell J.M., et al. Phosphodiesterase-4D knock-out and RNA interference-mediated knock-down enhance memory and increase hippocampal neurogenesis via increased cAMP signaling. J. Neurosci. 2011, 31:172-183.
53. Krause W., Kuhne G. Pharmacokinetics of rolipram in the rhesus and cynomolgus monkeys, the rat and the rabbit: studies on species differences. Xenobiotica 1988, 18:561-571.
54. Fujita M., Zoghbi S.S., Crescenzo M.S., Hong J., Musachio J.L., Lu J.Q., et al. Quantification of brain phosphodiesterase 4 in rat with (R)-[11C]Rolipram-PET. NeuroImage 2005, 26:1201-1210.
55. Lourenco C.M., Houle S., Wilson A.A., DaSilva J.N. Characterization of r-[11C]rolipram for PET imaging of phosphodieterase-4: in vivo binding, metabolism, and dosimetry studies in rats. Nucl. Med. Biol. 2001, 28:347-358.
56. Guo Q., Brady M., Gunn R.N. A biomathematical modeling approach to central nervous system radioligand discovery and development journal of nuclear medicine: official publication. Soc. Nucl. Med. 2009, 50:1715-1723.
57. Barnette M.S., Grous M., Cieslinski L.B., Burman M., Christensen S.B., Torphy T.J. Inhibitors of phosphodiesterase IV (PDE IV) increase acid secretion in rabbit isolated gastric glands: correlation between function and interaction with a high-affinity rolipram binding site. J. Pharmacol. Exp. Ther. 1995, 273:1396-1402.
58. Bollen E., Puzzo D., Rutten K., Privitera L., De Vry J., Vanmierlo T., et al. Improved long-term memory via enhancing cGMP-PKG signaling requires cAMP-PKA signaling. Neuropsychopharmacology 2014, 39:2497-2505.
59. Gil-Bea F.J., Solas M., Mateos L., Winblad B., Ramirez M.J., Cedazo-Minguez A. Cholinergic hypofunction impairs memory acquisition possibly through hippocampal Arc and BDNF downregulation. Hippocampus 2011, 21:999-1009.
60. Robinson L., Platt B., Riedel G. Involvement of the cholinergic system in conditioning and perceptual memory. Behav. Brain Res. 2011, 221:443-465.
61. Imanishi T., Sawa A., Ichimaru Y., Miyashiro M., Kato S., Yamamoto T., et al. Ameliorating effects of rolipram on experimentally induced impairments of learning and memory in rodents. Eur. J. Pharmacol. 1997, 321:273-278.
62. Schoffelmeer A.N., Wardeh G., Mulder A.H. Cyclic AMP facilitates the electrically evoked release of radiolabelled noradrenaline, dopamine and 5-hydroxytryptamine from rat brain slices. Naunyn-Schmiedeberg's Arch. Pharmacol. 1985, 330:74-76.