Nicotinic acetylcholine receptors in neurological and psychiatric diseases

被引:27
|
作者
Terry, Alvin V. [1 ,4 ]
Jones, Keri [2 ]
Bertrand, Daniel [3 ]
机构
[1] Med Coll Georgia Augusta Univ, Dept Pharmacol & Toxicol, Augusta 30912, Georgia
[2] Med Coll Georgia Augusta Univ, Educ Innovat Inst, Augusta 30912, Georgia
[3] HiQScreen Sarl, 6,Rte Compois, CH-1222 Geneva, Switzerland
[4] Augusta Univ, Dept Pharmacol & Toxicol, 1120 15th St,CB 3545, Augusta 30912, Georgia
关键词
Nicotine; Alzheimer's disease; Parkinson's disease; Schizophrenia; Depression; Anxiety; FRONTAL-LOBE EPILEPSY; ALPHA-BUNGAROTOXIN BINDING; MOUSE FORCED SWIM; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; TEMPORAL CORTEX; TRANSDERMAL NICOTINE; TOURETTES-SYNDROME; COGNITIVE FUNCTION; CIGARETTE-SMOKING;
D O I
10.1016/j.phrs.2023.106764
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that are widely distributed both pre- and post-synaptically in the mammalian brain. By modulating cation flux across cell membranes, neuronal nAChRs regulate neuronal excitability and the release of a variety of neurotransmitters to influence multiple physiologic and behavioral processes including synaptic plasticity, motor function, attention, learning and memory. Abnormalities of neuronal nAChRs have been implicated in the pathophysiology of neurologic disorders including Alzheimer's disease, Parkinson's disease, epilepsy, and Tourette ' s syndrome, as well as psychiatric disorders including schizophrenia, depression, and anxiety. The potential role of nAChRs in a particular illness may be indicated by alterations in the expression of nAChRs in relevant brain regions, genetic variability in the genes encoding for nAChR subunit proteins, and/or clinical or preclinical observations where specific ligands showed a therapeutic effect. Over the past 25 years, extensive preclinical and some early clinical evidence suggested that ligands at nAChRs might have therapeutic potential for neurologic and psychiatric disorders. However, to date the only approved indications for nAChR ligands are smoking cessation and the treatment of dry eye disease. It has been argued that progress in nAChR drug discovery has been limited by translational gaps between the preclinical models and the human disease as well as unresolved questions regarding the pharmacological goal (i.e., agonism, antagonism or receptor desensitization) depending on the disease.
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页数:15
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