title: α4β2* neuronal nicotinic receptor ligands (agonist, partial agonist and positive allosteric modulators) as therapeutic prospects for pain.
abstract: 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.
authors: In-Vivo Pharmacology, Discovery Research, Suven Life Sciences Ltd., Serene Chambers, Road No. 5, Avenue-7, Banjara Hills, Hyderabad 500034, India. nvsrk@suven.com
authors: Ramakrishna
authors: R
authors: Nirogi
authors: Venkatesh
authors: V
authors: Goura
authors: Renny
authors: R
authors: Abraham
authors: Pradeep
authors: P
authors: Jayarajan
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D054333:Drug Partial Agonism; D006801:Humans; D008024:Ligands; D018722:Nicotinic Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*
chemical_list: D008024:Ligands; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2