Rolipram and its optical isomers, phosphodiesterase 4 inhibitors, attenuated the scopolamine-induced impairments of learning and memory in rats

Japanese Journal of Pharmacology
T EgawaM Fujiwara

Abstract

We investigated the effects of (+/-)-rolipram, a phosphodiesterase (PDE) 4 inhibitor, and its isomers on scopolamine-induced deficits of learning and memory in rats using an 8-arm radial maze task and a passive avoidance task. 1) In the 8-arm radial maze task, (+/-)-rolipram (0.02-0.2 mg/kg, p.o.), (-)-rolipram (0.01-0.02 and 0.2-0.5 mg/kg, p.o.) and (+)-rolipram (20-50 mg/kg, p.o.) attenuated the scopolamine-induced deficits of spatial cognition. As for the minimum effective dose of each drug, (-)-rolipram was 2 and 2000 times as potent as (+/-)-rolipram and (+)-rolipram, respectively. (-)-Rolipram produced a biphasic dose-response and (+/-)-rolipram produced a broad dose-response. 2) (+/-)-Rolipram and its isomers also attenuated the scopolamine-induced deficits in the passive avoidance response. Also for the minimum effective dose, (-)-rolipram (0.01-0.02 mg/kg) was 2 and 200 times as potent as (+/-)-rolipram (0.02-0.1 mg/kg) and (+)-rolipram (2mg/kg). 3) The behaviorally effective doses of (+/-)-rolipram and its isomers also enhanced the oxotremorine-induced tremors in mice. Comparing these racemic isomers, (-)- and (+/-)-rolipram have more potent effects than (+)-rolipram on scopolamine-induced deficits in the 8-arm radial...Continue Reading

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Citations

Aug 19, 2008·Psychopharmacology·Olga A H ReneerkensJos Prickaerts
Sep 15, 2001·Brain Research. Developmental Brain Research·Y YeJ M O'Donnell
Aug 11, 2004·Behavioural Brain Research·Mauro GiorgiAntonella Gasbarri
Jul 26, 2013·Expert Opinion on Therapeutic Targets·Wito RichterMarco Conti
Jul 5, 2005·Expert Opinion on Investigational Drugs·H J Dyke, J G Montana
Sep 1, 2008·Expert Opinion on Drug Discovery·Arjan Blokland, Frank Boess
Feb 15, 2011·Pharmacology, Biochemistry, and Behavior·Alvin V TerryScott J Webster
Aug 23, 2011·Neuropharmacology·Joshua S RodeferSamuel J Eckrich
Jul 1, 2005·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Barbara MontiAntonio Contestabile
Sep 24, 1999·Pharmacology, Biochemistry, and Behavior·J S SilvestreJ M Palacios
Nov 23, 2012·ACS Chemical Neuroscience·Ana García-OstaRafael Franco

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