US EPA

2280133 

Journal Article 

alpha 4 beta 2*neuronal nicotinic receptor ligands (agonist, partial agonist and positive allosteric modulators) as therapeutic prospects for pain 

Nirogi, R; Goura, V; Abraham, R; Jayarajan, P 

2013 

1 

European Journal of Pharmacology
ISSN: 0014-2999
EISSN: 1879-0712 

712 

1-3 

22-29 

English 

23660369 

10.1016/j.ejphar.2013.04.021 

WOS:000320615900004 

α4β2* neuronal nicotinic acetylcholine receptor are ligand-gated ion channels and widely expressed throughout the central and peripheral nervous system. α4β2* neuronal nicotinic acetylcholine receptor play crucial role in pain signaling via modulation of multiple neurotransmitters like acetylcholine, dopamine, γ-amino butyric acid (GABA) and norepinephrine. Both spinal and supraspinal pathways are involved in the mechanisms by which α4β2* neuronal nicotinic acetylcholine receptor ligands modulate the neuropathic and inflammatory pain. Selective α4β2* neuronal nicotinic acetylcholine receptor ligands are being developed for the treatment of neuropathic and inflammatory pain as they show considerable efficacy in a wide range of preclinical pain models. Agonists/partial agonists of α4β2* neuronal nicotinic acetylcholine receptor show efficacy in animal models of pain and their anti-nociceptive properties are blocked by nicotinic antagonists. Positive allosteric modulators are being developed with the aim to increase the potency or therapeutic window of agonists/partial agonists. Accumulating evidences suggest that anti-nociceptive effects of nicotinic acetylcholine receptor ligands may not be mediated solely by α4β2* neuronal nicotinic acetylcholine receptor. We have also reviewed the stage of clinical development of various α4β2* neuronal nicotinic acetylcholine receptor ligands. 

alpha 4 beta 2*neuronal nicotinic acetylcholine receptor; Neuropathic pain; Inflammatory pain