Novel phosphodiesterase-5 inhibitors: Current indications and future directions

Sharma, Rashmi

doi:10.4103/0019-5359.37789

Cited by 31 publications

(26 citation statements)

References 35 publications

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“…Moreover, TAD is a PDE5 inhibitor with greater selectivity for PDE5; faster onset; and longer duration of action (Sharma 2007). TAD exerts its action by inhibiting PDE5 which increases the levels of intracellular cGMP (Lee et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Involvement of NO–cGMP pathway in anti-hyperalgesic effect of PDE5 inhibitor tadalafil in experimental hyperalgesia

Otari¹,

Upasani²

2015

Inflammopharmacol

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The association of elevated level of cyclic guanosine monophosphate (cGMP) with inhibition of hyperalgesia and involvement of nitric oxide (NO)-cGMP pathway in the modulation of pain perception was previously reported. Phosphodiesterases 5 (PDE5) inhibitors, sildenafil and tadalafil (TAD) used in erectile dysfunction, are known to act via the NO-cGMP pathway. TAD exerts its action by increasing the levels of intracellular cGMP. Hence, the present study investigated the effect of TAD 5, 10, or 20 mg/kg, per os (p.o.) or L-NAME 20 mg/kg, intraperitoneally (i.p.) and TAD (20 mg/kg, p.o.) in carrageenan- and diabetes-induced hyperalgesia in rats using hot plate test at 55 ± 2 °C. In carrageenan- and diabetes-induced hyperalgesia, TAD (10 and 20 mg/kg, p.o.) significantly increased paw withdrawal latencies (PWLs) as compared to the control group. L-NAME significantly decreased PWLs as compared to the normal group and aggravated the hyperalgesia. Moreover, significant difference in PWLs of L-NAME and TAD 20 was evident. Co-administration of L-NAME (20 mg/kg) with TAD (20 mg/kg) showed significant difference in PWLs as compared to the TAD (20 mg/kg), indicating L-NAME reversed and antagonized TAD-induced anti-hyperalgesia. This suggested an important role of NO-cGMP pathway in TAD-induced anti-hyperalgesic effect.

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Section: Introductionmentioning

confidence: 99%

Involvement of NO–cGMP pathway in anti-hyperalgesic effect of PDE5 inhibitor tadalafil in experimental hyperalgesia

Otari¹,

Upasani²

2015

Inflammopharmacol

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“…[1][2][3] However, these drugs have many side effects, such as headaches and visual impairment, which show that it is impending for further research with highly selective PDE5 inhibitor and for the development of natural drugs. 4 Investigations have suggested that the most metabolically active extract of Epimedium is icariin, which has been shown to exert inhibitory effects against PDE5.…”

Section: Introductionmentioning

confidence: 99%

Effect of icarisid II on diabetic rats with erectile dysfunction and its potential mechanism via assessment of AGEs, autophagy, mTOR and the NO–cGMP pathway

Zhang¹,

Li²,

Liu³

et al. 2012

Asian J Androl

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Erectile dysfunction (ED) is a major complication of diabetes mellitus. Icariin has been shown to enhance erectile function through its bioactive form, icarisid II. This study investigates the effects of icarisid II on diabetic rats with ED and its potential mechanism via the assessment of advanced glycosylation end products (AGEs), autophagy, mTOR and the NO-cGMP pathway. Icarisid II was extracted from icariin by an enzymatic method. In the control and diabetic ED groups, rats were administered normal saline; in the icarisid II group, rats were administered icarisid II intragastrically. Erectile function was evaluated by measuring intracavernosal pressure/mean arterial pressure (ICP/MAP). AGE concentrations, nitric oxide synthase (NOS) activity and cGMP concentration were assessed by enzyme immunoassay. Cell proliferation was analysed using methyl thiazolyl tetrazolium assay and flow cytometry. Autophagosomes were observed by transmission electron microscopy, monodansylcadaverine staining and GFP-LC3 localisation. The expression of NOS isoforms and key proteins in autophagy were examined by western blot. Our results have shown that Icarisid II increased ICP/MAP values, the smooth muscle cell (SMC) growth curve, S phase and SMC/collagen fibril (SMC/CF) proportions and decreased Beclin 1 (P,0.05). Icarisid II significantly increased the proliferative index and p-p70S6K(Thr389) levels and decreased the numbers of autophagosomes and the levels of LC3-II (P,0.01). Icarisid II decreased AGE concentrations and increased cGMP concentration, NOS activity (P,0.05) and cNOS levels (P,0.01) in the diabetic ED group. Therefore, Icarisid II constitutes a promising compound for diabetic ED and might be involved in the upregulation of SMC proliferation and the NO-cGMP pathway and the downregulation of AGEs, autophagy and the mTOR pathway.

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“…In addition to ED, their impact on several cardiovascular diseases, including pulmonary hypertension, heart failure, high-altitude pulmonary edema, Raynaud's phenomenon, coronary artery disease, diabetes mellitus, and atherosclerosis, has been shown [22][23][24]. As a nonselective phosphodiesterase inhibitor, pentoxifylline interferes with multiple cytokine pathways (TNF-a and TGF-b), which are involved in development of penile fibrosis and smooth muscle cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

The effect of pentoxifylline on penile cavernosal tissues in ischemic priapism-induced rat model

et al. 2014

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Novel phosphodiesterase-5 inhibitors: Current indications and future directions

Cited by 31 publications

References 35 publications

Involvement of NO–cGMP pathway in anti-hyperalgesic effect of PDE5 inhibitor tadalafil in experimental hyperalgesia

Involvement of NO–cGMP pathway in anti-hyperalgesic effect of PDE5 inhibitor tadalafil in experimental hyperalgesia

Effect of icarisid II on diabetic rats with erectile dysfunction and its potential mechanism via assessment of AGEs, autophagy, mTOR and the NO–cGMP pathway

The effect of pentoxifylline on penile cavernosal tissues in ischemic priapism-induced rat model

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