Medicinal nicotine in COVID-19 acute respiratory distress syndrome,the new corticosteroid

The cholinergic anti-inflammatory pathway (CAP) refers to the anti-inflammatory effects mediated by the parasympathetic nervous system. Existence of this pathway was first demonstrated when acetylcholinesterase inhibitors showed benefits in animal models of sepsis. CAP functions via the vagus nerve. The systemic anti-inflammatory effects of CAP converges on the α7 nicotinic acetylcholine receptor on splenic macrophages, leading to suppression of pro-inflammatory cytokines and simultaneous stimulation of anti-inflammatory cytokines, including interleukin 10. CAP offers a novel mechanism to mitigate inflammation. Electrical vagal nerve stimulation has shown benefits in patients suffering from rheumatoid arthritis. Direct agonists like nicotine and GTS-1 have also demonstrated anti-inflammatory properties in models of sepsis and acute respiratory distress syndrome, as have acetylcholinesterase inhibitors like Galantamine and Physostigmine. Experience with coronavirus disease 2019 (COVID-19) induced acute respiratory distress syndrome indicates that immunomodulators have a protective role in patient outcomes. Dexamethasone is the only medication currently in use that has shown to improve clinical outcomes. This is likely due to the suppression of what is referred to as a cytokine storm, which is implicated in the lethality of viral pneumonia. Nicotine transdermal patch activates CAP and harvests its anti-inflammatory potential by means of an easily administered depot delivery mechanism. It could prove to be a promising, safe and inexpensive additional tool in the currently limited armamentarium at our disposal for management of COVID-19 induced acute hypoxic respiratory failure.     

FDA对开发尼古丁替代疗法药品的要求

美国食品药品管理局（FDA）于2019年2月发布了"供企业用戒烟及相关适应症：开发尼古丁替代疗法药品的指导原则"（草案）。该指导原则介绍了FDA对尼古丁替代疗法（NRT）药品总体开发方案的建议，而我国目前尚无类似指导原则。介绍该指导原则的主要内容，期待对我国这类药的研发有益。     

The role of pituitary adenylyl cyclase activating polypeptide in affective signs of nicotine withdrawal

Recent evidence implicates endogenous pituitary adenylyl cyclase activating polypeptide (PACAP) in the aversive effect of nicotine. In the present study, we assessed if nicotine-induced conditioned place preference (CPP) or affective signs of nicotine withdrawal would be altered in the absence of PACAP and if there were any sex-related differences in these responses. Male and female mice lacking PACAP and their wild-type controls were tested for baseline place preference on day 1, received conditioning with saline or nicotine (1 mg/kg) on alternate days for 6 days and were then tested for CPP the next day. Mice were then exposed to four additional conditioning and were tested again for nicotine-induced CPP 24 hr later. Controls were conditioned with saline in both chambers and tested similarly. All mice were then, 96 hr later, challenged with mecamylamine (3 mg/kg), and tested for anxiety-like behaviors 30 min later. Mice were then, 2 hr later, forced to swim for 15 min and then tested for depression-like behaviors 24 hr later. Our results showed that male but not female mice lacking PACAP expressed a significant CPP that was comparable to their wild-type controls. In contrast, male but not female mice lacking PACAP exhibited reduced anxiety- and depression-like behaviors compared to their wild-type controls following the mecamylamine challenge. These results suggest that endogenous PACAP is involved in affective signs of nicotine withdrawal, but there is a sex-related difference in this response.