Phosphodiesterase Type-5 Inhibitors: A Critical Comparative Analysis
Section snippets
The phosphodiesterase (PDE): system
Currently the PDE system includes 11 families with a total of more than 50 splice variants (isoforms) [1], [2], [3], [4], [5]. The distribution and density of PDEs varies among the different tissues. The PDEs catalyse the breakdown either of cyclic guanosine monophosphate (cGMP) or of cyclic adenosine monophosphate (cAMP), which are both second messengers with specific physiologic functions. By hydrolysing the phosphodiesterase bond of cAMP or cGMP, respectively, these second messengers are
General considerations
A head to head comparison of the different PDE5 inhibitors is only possible and provides valuable and comparable data when all the three drugs were assessed under the same conditions. The IC50 values are in particular dependent on the following parameters:
Species and tissue being investigated, enzyme assay applied, substrate concentration (should be 10-fold lower than the target PDE), pH (buffer used?) of the milieu, in which the investigations were conducted.
The differences in the respective IC
Final conclusions on the three PDE5 inhibitors sildenafil, tadalafil and vardenafil
All three PDE5 inhibitors have shown a comparable efficacy profile with success rates of 70–75% (successful intercourse with maintenance of erection) in broad-spectrum ED populations. The efficacy profile declines in special subpopulations, such as diabetic patients and those after pelvic surgical procedures to a level of between 40 and 50%, depending on the severity of the underlying etiology and the procedure (radical or BNSP RRP) being performed, respectively [12], [14], [33]. According to
References (36)
- et al.
Expression of different phosphodiesterase genes in human cavernosum smooth muscle
J. Urol.
(2001) - et al.
The International Index of Erectile Function (IIEF): A multidimensional scale for assessment of erectile dysfunction
Urology
(1997) - et al.
Effect of Sildenafil in patients with erectile dysfunction taking antihypertensive therapy
Am. J. Hypertens.
(2001) - et al.
Clinical efficacy of sildenafil in patients on chronic dialysis
J. Urol.
(2001) - et al.
Efficacy of Tadalafil for the treatment of erectile dysfunction at 24 and 36 hours after dosing: A randomized controlled trial
Urology
(2003) - et al.
Efficacy and safety of tadalafil for the treatment of erectile dysfunction: Results of integrated analyses
J. Urol.
(2002) - et al.
4 year update on the safety of sildenafil citrate (Viagra®)
Urology
(2002) Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms
Physiol. Rev.
(1995)- Corbin JD, Francis SH, Webb D. Phosphodiesterase type 5 as a pharmacologic target in erectile dysfunction. Urology...
- et al.
Pharmacology of phosphodiesterase 5 inhibitors
IJCP
(2002)
Multiplicity within cyclic nucleotide phosphodiesterases
Biochemical Society Transactions
Sildenafil citrate for treatment of erectile dysfunction is similarily effective in men with type 1 and type 2 diabetes mellitus
Diabetes
Sildenafil for treatment of erectile dysfunction in men with diabetes
JAMA
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A comparison study of macrocyclic hosts functionalized reduced graphene oxide for electrochemical recognition of tadalafil
2017, Biosensors and BioelectronicsCitation Excerpt :Tadalafil is one of the three selective phosphodiesterase type 5 (PDE5) inhibitors, and it is the active compound of Cialis, a prescription drug approved by the United States Food and Drug Administration in 2003 for the treatment of erectile dysfunction (Ormrod et al., 2002; Giannitsas and Perimenis, 2009). The usage of these PDE5 inhibitors is controlled through medical supervision because of their harmful side effects such as headache, dyspepsia, back pain, rhinitis, and flu syndrome (Porst, 2004). Tadalafil has the disadvantage of poor aqueous solubility, which may cause formulation problems and lead to highly variable blood levels, and irreproducible clinical response (Badr-Eldin et al., 2008).
Dual β-cyclodextrin functionalized AuatSiC nanohybrids for the electrochemical determination of tadalafil in the presence of acetonitrile
2015, Biosensors and BioelectronicsCitation Excerpt :Tadalafil (Fig. 1A) is one of the three selective phosphodiesterase type 5 (PDE5) inhibitors, and it is the active compound of Cialis, a prescription drug approved by the United States Food and Drug Administration in 2003 for the treatment of erectile dysfunction (Giannitsas and Perimenis, 2009). The usage of these PDE5 inhibitors is controlled through medical supervision because of their harmful side effects such as headache, dyspepsia, back pain, rhinitis, and flu syndrome (Porst, 2004). Numerous analytical techniques have been used to quantify pharmaceutical analysis of tadalafil, including HPLC with fluorescence (Farthing et al., 2010), GC–MS (Nikolaou et al., 2011), immunoassay (Guo et al., 2010a), and a combination of different methods.
Determination of sildenafil, vardenafil and aildenafil in human plasma by dispersive liquid-liquid microextraction-back extraction based on ionic liquid and high performance liquid chromatography-ultraviolet detection
2013, Journal of Chromatography B: Analytical Technologies in the Biomedical and Life SciencesCitation Excerpt :These drugs were also deliberately added in dietary supplement [8–10], herbal products [11,12] and health care products [13]. If people take these drugs unreasonably, adverse effects, such as headache, vertigo, the reduction of blood pressure and aggravation of cardiovascular disease [14–16], may emerge. It is thus important to monitor the concentration level in biological samples for clinical or forensic purposes [17–19].
Magnetic molecularly imprinted polymer for the selective extraction of sildenafil, vardenafil and their analogs from herbal medicines
2013, TalantaCitation Excerpt :In recent years, these herbal alternatives have been found containing synthetic PDE-5 inhibitors as adulterants [1–4], such as sildenafil, vardenafil, tadalafil, methisosildenafil, etc. Although three PDE-5 inhibitors approved by the European Medicines Agency (EMA) and Food and Drug Administration (FDA) appear to be relatively safe, their illicit usage is still worrying because of harmful side-effects such as headache, flush, dyspepsia, rhinitis, back pain [5]. However, there are reports that even the unapproved synthetic analogs of PDE-5 inhibitors have been found in herbal dietary supplements [3,4,6] such as homosildenafil, hydroxyhomosildenafil, methisosildenafil, acetildenafil, etc.
South African plants and male reproductive healthcare: Conception and contraception
2012, Journal of EthnopharmacologyCitation Excerpt :Sperm abnormalities include; lack of sperm, too little sperm, abnormal sperm morphology and insufficient sperm motility (Feng, 2003). Sexual dysfunction includes; disorders of desire, disorders of ejaculation and orgasm, erectile dysfunction and failure of detumescence (Porst, 2004 cited in Singh et al., 2010). In South Africa, male causal factors accounts for 40% of total infertility or failure to achieve pregnancy (Jacobson, 2010).
Discovery of potent, selective, and orally bioavailable PDE5 inhibitor: Methyl-4-(3-chloro-4-methoxybenzylamino)-8-(2-hydroxyethyl)-7-methoxyqui nazolin-6-ylmethylcarbamate (CKD 533)
2010, Bioorganic and Medicinal Chemistry Letters