Nicotinic simulations

Assays of acetyl- and butyrylcholine esterases inhibition, as well as of modulation of calcium channels and nicotinic receptors have been conducted in vivo. Moreover, their interaction with the active center of acetylcholine esterase has been simulated by molecular dynamics. For synthesized compounds the IC50 of acetylcholine esterase inhibition was about 9 X M, and for the most active the value was four to five times... 

Automobile and truck simulators have also been used in randomized studies to demonstrate the impairing effects of various doses of alcohol.78-80 Similar studies have been conducted using flight simulators.81-85 In addition, both types of simulators have been used to assess the effects of marijuana, nicotine, and other sedative medications.86-88 Simulations have also been used to examine other environmental perturbations, including sleep deprivation and elevated carbon dioxide levels.89,90... 

Mumenthaler, M.S. et al., Influence of nicotine on simulator flight performance in non-smokers, Psychopharmacology, 140, 38, 1998. 

Acetylcholine receptors. There are numerous receptors for ACh (Fig. 12—10), of which the major subtypes are nicotinic and muscarinic subtypes of cholinergic receptors. Classically, muscarinic receptors are simulated by the mushroom alkaloid muscarine and nicotinic receptors by the tobacco alkaloid nicotine. Nictotinic receptors are all ligand-gated, rapid-onset, and excitatory ion channels, which are blocked by curare. Muscarinic receptors, by contrast, are G protein—linked, can be excitatory or inhib-... 

Nicotinic acid can cause hepatic steatosis and clinical hepatic abnormalities that together can simulate the presentation of hepatobiliary neoplasia (36). 

Grady SR, Murphy KL, Cao J, Marks MJ, McIntosh JM, Collins AC (2002) Characterization of nicotinic agonist-induced [(3)H]dopamine release from synaptosomes prepared from four mouse brain regions. J Pharmacol Exp Ther 301 651-60 Graham B, Redman S (1994) A simulation of action potentials in synaptic boutons during presynaptic inhibition. J Neurophysiol 71 538 49... 

Models of the nicotinic acetylcholine receptor consisting of the five M2 helices that form the pore have been investigated in a series of MD simulations [94]. The behavior of single helices in water and in lipid was compared, and the a-helical structure was again found to be stabilized by the membrane. Two simulations of bundles of five M2 helices forming a pore and differing in the ionization state of the ionizable amino acid residues were performed. When these residues were included in their ionized states, the bundle expanded over the 2 ns of the simulation, while it remained stable if calculated pit, values were used to determine the ionization states of ionizable residues. In these simulations structural fluctuations were also observed on a several hundred picosecond time scale that transiently closed the pore. 

Although CO2 is the most commonly used supercritical fluid for extraction, the solubility of certain solutes in CO2 is usually low and causes an inconvenience. The remedy for this problem is to add some entrainers such as water to facilitate the extraction. In this background, the MD simulations were carried out to study the supercritical extraction of nicotine by CO2 in the presence and absence of water as entrainer[40]. In the tobacco leaf, nicotine molecule is bonded to other organic molecules and forms organic acid salts. The malic salts of nicotine was chosen as the model with nicotine bonded to two malic molecules by hydrogen bonds[41]. It is assumed that when malic salts of nicotine are extracted from tobacco leaf, supercritical CO2 or entrainer molecule attacks the hydrogen bonds and decomposes the salt into three molecules. 

The role of water as entrainer in the extraction of nicotine by supercritical CO2 fluid was studied by MD simulation. The following three systems were studied in detail ... 

The dynamic behaviour of the system h (nicotine salt and CO2 supercritical fluid) and the system c (system b plus entrainer molecules) is shown in Figs. 18a and 18b, respectively. It can be seen from these CG pictures that the malic salts of nicotine keeps its configuration even on interaction with the supercritical CO2 and the two hydrogen bonds remain stable during the simulation (Fig. 18a). On the contrary, the separation of nicotine from its malic counterparts develops in the presence of entrainer molecules and hydrogen bonds become finally broken (Fig. 18b). 

Interestingly, unlike simple, classic competitive models, increasing drug concentration C will not overcome the inhibitor s effect Tol because Tol will increase proportionately—defeating the gains of increased drug concentration. This model has been used to simulate nicotine tolerance (61), multiple intravenous bolus dose morphine tolerance (64), and tolerance to caffeine s pressor effects (63). 

Klus et al. (15A32) measured several ETS-related TSNAs in indoor air of an 83-m office under various smoking conditions. NNN varied from 0.7 to 6 pg/L, NNK varied from 0.2 to 10.7 pg/L. They found no correlation with the carbon monoxide levels. Tricker et al. (3945) reported that nicotine was not V-nitrosated to NNN under simulated gastric conditions. However, nomicotine, anabasine, and anatabine were V-nitrosated to NNN, NAB, and NAT, respectively, under such conditions. They also reported that NNK decomposed slightly under these conditions. 

Ingebrethsen, B.J. An investigation of nicotine mass transport during smoking using a model aerosol computer simulation 59th Tobacco Science Research Conference, Program Booklet and Abstracts, Vol. 59, Paper No. 60, 2005, p. 51. 

Bupropion appears to reduce nicotine withdrawal symptoms and may simulate the actions of nicotine on the brain reward system. The most common side-effects related to bupropion are insomnia (30-45% at a dose of 300 mg/day) and dry mouth. Other commonly reported adverse events include hypertension, headache, and nausea. Seizures are a known risk associated with the use of somewhat higher doses compared with other antidepressants (0.1-0.4%), especially for the immediate-release form of the drug and when given at dosages of 450 mg/day or higher. Bupropion, unlike the TCAs, is virtually free of adverse cardiovascular effects, which makes it quite attractive for specific populations. 

To model the chance probabilities of obtaining positive maikers as close to markers previously reported to be linked to ethanol or nicotine addiction, we used more than 100 million simulation trials in which 61 markers were randomly positioned on a 3.2 billion bp genome, then 31 markers randomly placed on the same genome and pairwise distances between each marker pair, consisting of one member of the first set and one monber of the second set, were determined. 

Nicotine (for smoking habit) Nicotine concentration is simulated ... 

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