Sodium channel blockers for neuropathic pain.
BACKGROUND
The voltage-gated sodium channels (VGSCs) play a fundamental role in controlling cellular excitability and their abnormal activity is related to several pathological processes, including cardiac arrhythmias, epilepsy, neurodegenerative diseases, spasticity, chronic and neuropathic pain. In particular, neuropathic pain (e.g., postherpetic and trigeminal neuralgia, diabetic neuropathy and spinal cord injury) is a serious clinical problem that affects a high percentage of the world population. Because an altered sodium channel isoform expression profile has been considered one reason for the changes in neuronal excitability, there is a continuous quest for new selective molecules targeting sodium channels for the treatment of chronic pain.


METHODS
PubMed, http://www.sciencedirect.com/ , SciFinder Scholar and http://ep.espacenet.com/ were used as sources for this review and patents between 2007 and September 2009 were taken into account for the sodium channel blockers molecular classes reviewed and discussed herein.


RESULTS
The sodium channel blockers reported in this review have been categorized into different molecular classes on the basis of their wide structural diversity. This classification, somewhat arbitrary, does not necessarily reflect the presence of pharmacophoric elements but offers a useful way to discuss and comment on structurally homogenous classes of chemotypes recently patented.


CONCLUSIONS
The continuous discoveries in the field of sodium channel blockers, highlighted by the increasing numbers of patent applications published in the last few years and by the numbers of compounds currently in clinical development, underline the importance of this target for the treatment of neuropathic pain. The great difficulty in the design of new selective and active structures, not obtained from old VGSC blockers that are often associated with high risk of adverse effects, is a strong challenge for medicinal chemistry research.
Zuliani
Valentina
V
Dipartimento Farmaceutico, Università degli Studi di Parma, V.le G.P. Usberti 27/A, I-43124 Parma, Italy. valentina.zuliani@unipr.it
Rivara
Mirko
M
Fantini
Marco
M
Costantino
Gabriele
G
D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002908:Chronic Disease; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D009437:Neuralgia / Q000188:drug therapy* / Q000503:physiopathology; D010330:Patents as Topic; D026941:Sodium Channel Blockers / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism
D000700:Analgesics; D026941:Sodium Channel Blockers; D015222:Sodium Channels