TABLE 4.
List of synthetic drugs for PDE inhibitors and their impact on clinical significance with a focus on Alzheimer’s disease.
| FDA approved drug | PDE type | Clinical significance |
| Vinpocetine | PDE1 | Improve memory in people with mild cognitive impairment (MCI), dementia, memory loss (Prickaerts et al., 2017). |
| Theophylline | PDE | Theophylline is a non-selective phosphodiesterase (PDE) inhibitor (Chen et al., 2008). |
| Propentofylline | PDE | Propentofylline is used to treat canine cognitive impairment, which is caused by age-related wild-type Aβ deposition, similar to Alzheimer’s disease. Phosphodiesterase inhibitors may help to prevent and treat Alzheimer’s disease (Sanders and Rajagopal, 2020). |
| Nimodipine | PDE1 and 2 inhibitors | Nimodipine is a dihydropyridine that inhibits PDE1 and antagonizes/blocks primarily L-type Ca2+ channels (Lugnier, 2006). |
| Lu AF64280 | PDE2 and 10 inhibitors | Lu AF64280 is a new phosphodiesterase (PDE) 2A inhibitor that is brain penetrant and selective. In vivo models/tests relevant to cognitive processing or antipsychotic-like effects, as well as in vitro/in vivo assays indicative of PDE2A inhibition (Redrobe et al., 2014). |
| Lu AF33241 | Lu AF33241, a new brain-penetrant phosphodiesterase inhibitor of (PDE) 2A and 10A tool compound, in vivo models/tests related to cognitive processing and antipsychotic-like activity, and in vitro/in vivo assays indicative of PDE2A and/or PDE10A inhibition (Redrobe et al., 2014; John et al., 2015). | |
| Cilostazol | PDE 3 inhibitor | In a mouse model of Alzheimer’s disease, cilostazol, a selective inhibitor of phosphodiesterase (PDE) 3, promotes amyloid β clearance and alleviates cognitive deficits (Tsuji et al., 2020). |
| Rolipram | PDE4 inhibitor | Rolipram, a phosphodiesterase-4 inhibitor, was studied in mice to see if it could help with cognitive deficiencies caused by streptozotocin and normal aging. It may improve with memory problems due to its anti-cholinesterase, anti-amyloid, anti-oxidant, and anti-inflammatory properties (Kumar and Singh, 2017). |
| Zaprinast | PDE5 inhibitor | Prickaerts et al. (1997) found that the PDE5 inhibitor zaprinast significantly increased performance in an ORT while not affecting peripheral vascular function (Prickaerts et al., 1997; Rutten et al., 2009). |
| Sildenafil/Tadalafil | PDE 5 | The PDE5 inhibitor sildenafil has powerful anti-AD benefits, reversing cognitive decline (García-Osta et al., 2012). The capacity of PDE5 inhibitors to increase cGMP levels and so interfere with the NO/cGMP/PKG/CREB signaling pathway has led to the concept that PDE5 inhibition could be employed as a viable therapeutic method for the treatment of AD (Zuccarello et al., 2020). |
| Zaprinast, Dipyridamole Vardenafil | PDE 6 | Transducin-activated (Ghosh et al., 2009). |
| Dipyridamole, Thiadiazole | PDE 7 | Rolipram-insensitive, IBMX-insensitive (Ghosh et al., 2009). |
| Dipyridamole | PDE 8 | |
| PF-04447943 | PDE9 inhibitor | PF-04447943 is a powerful, selective brain penetrant PDE9 inhibitor that improved cognitive function and raised indications of hippocampal synaptic plasticity in a range of cognition models in rats and mice (Hutson et al., 2011). |
| Mp-10 (PF-2545920) | PDE 10A inhibitor | The selective antagonist MP-10 inhibits phosphodiesterase 10A, which stimulates dopamine D2 receptor-expressing medium spiny neurons more than D1 receptor-expressing neurons (Wilson et al., 2015). |
| Zaprinast and dipyridamole | PDE 11 inhibitor | PDE11A is sensitive to non-selective PDE inhibitors, as well as zaprinast and dipyridamole, inhibitors that are thought to be more specific for cGMP-selective PDEs (Fawcett et al., 2000). |
| Tacrine | PDE | Substantial cAMP PDE inhibition (Curley et al., 1984). |