Phosphodiesterase type

Erectile dysfunction is treated by local or systemic application of vasodilator drugs. The most effective is sildenafil, a phosphodiesterase-type 5 inhibitor. 

Phosphodiesterase type 5 inhibitors are commonly prescribed for erectile dysfunction and include sildenafil, vardenafil,... 

Van Staveren, W., Steinbusch, H. W. M., Markerink-Van Ittersum, M. et al. mRNA expression patterns of the cGMP-hydrolysing phosphodiesterases types 2, 5, and 9 during development of the rat brain. /. Comp. Neurol. 467 566-580, 2003. 

R)-(-)-baclofen 58,138 and phosphodiesterase type IV inhibitor, (R)-(—)-rolipram 59,187 were efficiently prepared with an intramolecular G-H insertion being used as a key step (Equations (49) and (50)). 

Viagra (sildenafil) Phosphodiesterase type 5 inhibitor Mort and Brigitte Harris Foundation Phase I... 

Drugs that affect all phosphodiesterase type 5 inhibitors include the following alcohol, amlodipine, angiotensin II receptor blockers, antacids, bendroflumethiazide, beta blockers, cimetidine, diuretics, enalaphl, metoprolol, nifedipine, rifampin, tacrolimus. 

Drugs that may be affected by itraconazole include alfentanil, almotriptan, alprazolam, amphotericin B, aripiprazole, benzodiazepines, buspirone, busulfan, calcium blockers, carbamazepine, cilostazol, cisapride, corticosteroids, cyclosporine, digoxin, disopyramide, docetaxel, dofetilide, eletriptan, epierenone, ergot alkaloids, haloperidol, HMG-CoA reductase inhibitors, hydantoins (phenytoin), hypoglycemic agents, oral midazolam, phosphodiesterase type 5 inhibitors, pimozide, polyenes, protease inhibitors, quinidine, rifamycins, sirolimus, tacrolimus, tolterodine, triazolam, trimetrexate, vinca alkaloids, warfarin, and zolpidem. 

Drugs that may be affected by indinavir include antiarrhythmics, clarithromycin, dihydropyridine calcium channel blockers, HMG-CoA reductase inhibitors, immunosuppressant agents, phosphodiesterase type 5 inhibitors, pimozide, saquinavir, trazodone, cisapride, amiodarone, benzodiazepines, ergot alkaloids, fentanyl, rifamycins, ritonavir. 

Antunes, J.E., Freitas, M.P., da Cunha, E.F.F., Ramalho, T.C., Rittner, R. In silico prediction of novel phosphodiesterase type-5 inhibitors derived from sildenafil, vardenafil and tadalafil. Bioorg. Med. Chem. 2008, 16, 7599-606. 

The enzyme phosphodiesterase (type III) catalyzes the biode-gradation of cyclic AMP (cAMP). Inhibition of this enzyme will cause accumulation of the nucleotide cAMP and hence induces an increase in cardiac contractile force. This effect does not involve cardiac jS-adrenoceptors and will therefore persist after downregulation of these receptors associated with heart failure. 

L A. The principal action of sildenafil is selective inhibition of the enzyme phosphodiesterase type 5. 

Mechanism of Action An erectile dysfunction agent that inhibits phosphodiesterase type 5, the enzyme responsible for degrading cyclic guanosine monophosphate (cGMP) in the corpus cavernosum of the penis and pulmonary vascular smooth muscle, resulting in smooth muscle relaxation and increased blood flow. Therapeutic Effects Facilitates an erection, produces pulmonary vasodilation. 

Phosphodiesterase Type 5 (PDE5) inhibitors sildenafil citrate... 

Sildenafil It is orally active selective inhibitor of phosphodiesterase type 5 useful in treatment of erectile dysfunction. It results in reduced breakdown of cyclic guanosine monophosphate (cGMP) which is responsible for nitric acid (NO) mediated vasodilatation in corpora cavernosa. Thus inducing an erectile response to sexual stimulation. It has no direct relaxant effect on smooth muscle of corpus cavernosa and has no effect in absence of sexual stimulation. 

It is a relatively selective inhibitor of cyclic GMP, cyclic AMP-PDE (phosphodiesterase) type 111 family. It causes vasodilatation with a consequent decrease in systemic vascular resistance. It increases both the force of contraction and velocity of relaxation of cardiac muscles. It is administered IV 0.75 mg/kg/min as a bolus dose followed by 5-10 pg/kg/min IV infusion and total dose not to exceed 10 mg/kg. 

Venodilators Releases nitric oxide (NO) activates guanylyl cyclase (see Chapter 12) Venodilation reduces preload and ventricular stretch Acute and chronic heart failure angina Oral 4-6 h duration Toxicity Postural hypotension, tachycardia, headache Interactions Additive with other vasodilators and synergistic with phosphodiesterase type 5 inhibitors... 

Inamrinone, milrinone Phosphodiesterase type 3 inhibitors decrease cAMP breakdown Vasodilators lower peripheral vascular resistance also increase cardiac contractility Acute decompensated heart failure IV only duration 3-6 h Toxicity Arrhythmias Interactions Additive with other arrhythmogenic agents... 

Another group of thalidomide analogs, selective cytokine inhibitory drugs (SelCIDs), are phosphodiesterase type 4 inhibitors with potent anti-TNF-a activity but no T-cell co-stimulatory activity. Several SelCIDs are currently under investigation for clinical use. 

PDE5 phosphodiesterase type 5 drugs used to treat conditions such as erectile dysfunction, e.g., sildenafil, interfere with this enzyme... 

Normally, the desire to have sexual relations is a powerful message sent from the brain down the spinal cord and through peripheral nerves to smooth muscle cells in the penis, triggering them to produce sufficient nitric oxide to form all the cyclic GMP necessary to create an erection (Fig. 14—11). The cyclic GMP lasts long enough for sexual intercourse to occur, but then phosphodiesterase (type V in the penis) eventually breaks down the cGMP (Fig. 14—5), and the erection is lost (called detumescence). 

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