Role of sildenafil in neurological disorders.
Sildenafil, a phosphodiesterase-5 inhibitor commonly used for erectile dysfunction, may also have a beneficial therapeutic effect in the treatment of stroke, subarachnoid hemorrhage, dementia, learning, and neurodegenerative disorders by enhancing angiogenesis and neurogenesis. It also favorably influences the nitric oxide-cyclic guanosine monophosphate pathways, which are involved in the pathogenesis of a number of neurological diseases. Its potential therapeutic role in the treatment of the neurological disorders mentioned above is still under preclinical investigation. Sildenafil is currently being used to treat erectile dysfunction in patients with multiple sclerosis, Parkinson disease, multisystem atrophy, and spinal cord injury by improving their neurologically related erectile dysfunction. Conversely, it has been implicated in a number of neurological problems, such as intracerebral hemorrhage, migraine, seizure, transient global amnesia, nonarteritic anterior ischemic optic neuropathy, macular degeneration, branch retinal artery occlusion, and ocular muscle palsies. Thus, preclinical and very limited clinical data suggest that sildenafil may have therapeutic potential in selected neurological disorders. However, numerous reports are available regarding neurological adverse events ascribed to the drug. Although sildenafil shows some promise as a therapeutic agent in selected neurological disorders, well-designed clinical trials are needed before the agent can be recommended for use in any neurological disorder.
Farooq
Muhammad U
MU
Department of Neurology and Ophthalmology, Michigan State University, East Lansing, MI, USA.
Naravetla
Bharath
B
Moore
Philip W
PW
Majid
Arshad
A
Gupta
Rishi
R
Kassab
Mounzer Y
MY
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D002490:Central Nervous System / Q000201:enzymology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D007172:Erectile Dysfunction / Q000188:drug therapy; D006801:Humans; D008297:Male; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D010879:Piperazines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011687:Purines / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000493:pharmacokinetics / Q000627:therapeutic use*
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D009569:Nitric Oxide; D000068677:Sildenafil Citrate; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases