Current approaches with the glutamatergic system as targets in the treatment of neuropathic pain.
Glutamate is the most widely distributed and a major excitatory neurotransmitter in the CNS. It has been found to play a critical role in various physiological functions in which increased glutamate or its subsequent stimulation is thought to have a role in pathophysiological mechanism of various CNS diseases like epilepsy, stroke, depression and pain. Early attempts to develop glutamatergic antagonists failed in clinical studies due to nonselective or competitive antagonism and have a lot of safety issues like loss of cognitive functions, psychomimetic effect and sedation. Neuropathic pain can be described as pain associated with damage or permanent alteration of the peripheral or central nervous system. At present, there are very few effective therapies for neuropathic pain. The current approach includes targeting specific or alternate binding sites of glutamate receptors, resulting in reduced CNS liabilities. Targeting the glutamatergic system shows a better efficacy and fewer side effects, compared with classical drugs for the treatment of neuropathic pain. This review discusses the various targets on glutamatergic system, which includes the receptors, transporters and enzymes, for the treatment of neuropathic pain and their advantages over classical glutamatergic antagonists. The review also highlights the newer drugs in clinical trials for neuropathic pain.
Yogeeswari
Perumal
P
BITS-Pilani, Hyderabad Campus, Pharmacy, Shameerpet mandal, Jawahar Nagar, RR District, 500078, Hyderabad, India. pyogie_2000@rediffmail.com
Semwal
Arvind
A
Mishra
Ramkumar
R
Sriram
Dharmarajan
D
D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D018698:Glutamic Acid / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D016896:Treatment Outcome
D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid