Effects of two selective phosphodiesterase type 5 inhibitors, sildenafil and vardenafil, on object recognition memory and hippocampal cyclic GMP levels in the rat

Prickaerts, Jos; Staveren, Wilma C.G. van; Şık, Ayhan; Ittersum, Marjanne Markerink‐van; Niewöhner, Ulrich; Staay, Franz Josef van der; Blokland, Arjan; Vente, Jan de

doi:10.1016/s0306-4522(02)00199-9

Cited by 209 publications

(154 citation statements)

References 31 publications

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“…The NO/cGMP pathway seems to play a role 20 Moreover, incubation of rat hippocampal slices with vardenafil results in an increase of cGMP. 21 Some authors have shown that NO decreases the central sympathetic output to the periphery 22 through a cGMP-dependent mechanism or through interactions with other neurotransmitters. 23 Many lines of evidence support the presence and activity of the NO/cyclic guanosine monophosphate (cGMP) and NO/cyclic adenosine monophosphate (cAMP) signaling pathways in the seminal vesicle (SV), 24 smooth muscles, prostate and urethra.…”

Section: Discussionmentioning

confidence: 99%

Effects of vardenafil administration on intravaginal ejaculatory latency time in men with lifelong premature ejaculation

et al. 2009

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Premature ejaculation (PE) is thought to be the most common male sexual dysfunction; however, the prevalence of lifelong (LL)-PE is relatively low. The aim of this study was to investigate the effects of on-demand vardenafil (10 mg) to modify the intravaginal ejaculatory latency time (IELT) in men with LL-PE without erectile dysfunction. Forty-two men (18-35 years) were enrolled in a 16-week, double-blind, placebo-controlled, cross-over study. Primary end point was the modification from baseline of IELT assessed by stopwatch technique; secondary end points were post-ejaculatory refractory time (PERT) and variations of scores at the Index of Premature Ejaculation questionnaire. The changes in geometric mean IELT were superior after taking vardenafil (0.6±0.3 vs 4.5 ± 1.1 min, Po0.01), compared with placebo (0.7 ± 0.3 vs 0.9 ± 1.0 min, ns). PERT dropped significantly after vardenafil (16.7 ± 2.0 vs 4.3 ± 0.9 min, Po0.001), compared with placebo (15.3±2.2 vs 15.8±2.3 min). Patients who took vardenafil (vs placebo) reported significantly (Po0.01) increased ejaculatory control (6±2 vs 16±2), improved overall sexual satisfaction (7±2 vs 15 ± 1) and distress (4 ± 1 vs 8 ± 1) scores, respectively. Multiple regression analysis (r 2 ¼ 0.86) for IELT by the number of attempts at sexual intercourse showed significant differences between the slopes of lines for placebo and vardenafil (Po0.0001). The most common adverse events for vardenafil (vs placebo) were headache (10 vs 3%), flushing (12 vs 0%) and dyspepsia (10 vs 0%), which tended to disappear over the time. In conclusion, in our study, vardenafil increased IELT and reduced PERT in men with LL-PE. Besides, improvements in confidence, perception of ejaculatory control and overall sexual satisfaction were reported.

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Section: Discussionmentioning

confidence: 99%

Effects of vardenafil administration on intravaginal ejaculatory latency time in men with lifelong premature ejaculation

et al. 2009

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“…Figure 1a illustrates the effects of these sildenafil treatments on the index of discrimination d2. This experiment was part of another study (Prickaerts et al 2002b). No differences were found between the different doses in the total level of exploration in T1 [e1; F(3,30)=1.08, n.s.].…”

Section: Metrifonatementioning

confidence: 99%

“…One group was used for testing the effects of sildenafil administration immediately after the first trial in the object recognition test. This experiment was part of another study (see Prickaerts et al 2002b). Subsequently, all 24 rats were used for the sildenafil treatment 30 min before the first trial.…”

Section: Treatmentsmentioning

confidence: 99%

“…It has been shown that administration of zaprinast, sildenafil or vardenafil, which are inhibitors of the phosphodiesterase enzyme type 5 (PDE5) that selectively breaks down cyclic GMP (cGMP), improves the performance of adult rats in an object recognition task (Prickaerts et al 1997(Prickaerts et al , 2002b. This suggests that PDE5 inhibitors may have cognition-enhancing properties.…”

Section: Introductionmentioning

confidence: 99%

“…Of note, administration of a drug before the learning trial may also have an effect on consolidation and even on retention, depending on its pharmacokinetic properties. Since all PDE5 inhibitors in previous studies were always administered immediately after the learning trial, it was concluded that processes of early consolidation of object information are influenced (Prickaerts et al 1997(Prickaerts et al , 2002b.…”

Section: Introductionmentioning

confidence: 99%

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Dissociable effects of acetylcholinesterase inhibitors and phosphodiesterase type 5 inhibitors on object recognition memory: acquisition versus consolidation

Prickaerts

Şık

Staay³

et al. 2004

Psychopharmacology

126

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Rationale: Phosphodiesterase enzyme type 5 (PDE5) inhibitors and acetylcholinesterase (AChE) inhibitors have cognition-enhancing properties. However, it is not known whether these drug classes affect the same memory processes.Objective: We investigated the memory-enhancing effects of the PDE5 inhibitor sildenafil and AChE inhibitors metrifonate and donepezil in the object recognition task to find out whether acquisition or consolidation processes were affected by these drugs. Methods: The object recognition task measures whether rats remembered an object they have explored in a previous learning trial. All drugs were given orally 30 min before or immediately after learning to study acquisition and consolidation, respectively. Results: Sildenafil given immediately after the first trial improved the memory performance after 24 h and resulted in an inverted U-shaped dose-effect curve with the peak dose at 3 mg/kg. When given before the first trial, sildenafil also improved the memory performance. However, the dose needed for the best performance under this condition was 10 mg/kg, suggesting that the dose-effect curve shifted to the right. This can be explained by the metabolic clearance of the high dose of sildenafil. Donepezil had no memory improving effect when given after the first trial. However, when given before the first trial, a gradually increasing dose-effect curve was found which had its maximum effect at the highest dose tested (1 mg/kg). Likewise, only when metrifonate (30 mg/kg) was given before the first trial did rats show an improved memory performance. Conclusion: Our data strongly suggest that PDE5 inhibitors improve processes of consolidation of object information, whereas AChE inhibitors improve processes of acquisition of object information.

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Novel Object Recognition in the Rat: A Facile Assay for Cognitive Function

Mathiasen¹,

DiCamillo²

2010

CP Pharmacology

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The rat novel object recognition (NOR) assay is a relatively high-throughput, robust, and sensitive procedure for evaluating compounds for cognition-enhancing activity. For the test, rats are given the opportunity to explore two identical objects for a predetermined period of time. After a delay, the animals are then presented with two objects to explore, one of which is the same as in the first exploration trial, the other a new object. Depending on the length of the delay between the two trials, the rats will either explore the novel object for a greater time period, indicating memory for the familiar object, or will explore the novel and familiar objects for the same amount of time, indicating a lack of recall or loss of memory for the familiar object presented during the initial trial. The protocol described in this unit can be used to evaluate the effects of a compound on the short-term/working memory of adult male rats following a 24-hr inter-trial interval.

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Effects of two selective phosphodiesterase type 5 inhibitors, sildenafil and vardenafil, on object recognition memory and hippocampal cyclic GMP levels in the rat

Cited by 209 publications

References 31 publications

Effects of vardenafil administration on intravaginal ejaculatory latency time in men with lifelong premature ejaculation

Effects of vardenafil administration on intravaginal ejaculatory latency time in men with lifelong premature ejaculation

Dissociable effects of acetylcholinesterase inhibitors and phosphodiesterase type 5 inhibitors on object recognition memory: acquisition versus consolidation

Novel Object Recognition in the Rat: A Facile Assay for Cognitive Function

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