• agonist
  • Thus, we and others have begun investigations to identify the structureactivity relationships (SAR) for nicotinic agonist and antagonist activity, and structure-affinity relationships (SAFIR) for central nAChR binding, to ultimately develop novel nicotinic agents with greater selectivity and reduced toxicity that may be useful for disorders involving nAChRs. (springer.com)
  • Changes in the response to a concomitantly administered adrenergic agonist or antagonist should be watched for when nicotine intake is altered during Nicotrol Inhaler therapy and/or smoking cessation (See PRECAUTIONS, Drug Interactions ). (drugs.com)
  • 3-Bromocytisine Acetylcholine Cytisine Galantamine Epibatidine Epiboxidine Nicotine A-84,543 A-366,833 ABT-418 Altinicline Dianicline Ispronicline Pozanicline Rivanicline Tebanicline TC-1827 Varenicline Sazetidine A: full agonist on (α4)2(β2)3, 6% efficacy on (α4)3(β2)2 N-(3-pyridinyl)-bridged bicyclic diamines NS-9283: 60-fold left-shifting of concentration-response curve, no change in maximum efficacy Desformylflustrabromine Further compounds. (wikipedia.org)
  • pathways
  • However, in breast tumors, the α9 subunit is the most abundant nAChR, and downstream signaling pathways such as MAPK and PI3K/Akt can be activated through nicotine and E2 stimulation. (aacrjournals.org)
  • The downstream transcription factors AP1 and VDR can bind the promoter region of α9-nAChR by activating the ER at Ser-167 and Ser-118, or at Ser-104/106 sites through the PI3K/Akt and MAPK pathways. (aacrjournals.org)
  • The changes were greatest in teenagers who smoked, suggesting the brain is particularly vulnerable to the effects of nicotine during adolescence, when many neural pathways are maturing (Journal of Neuroscience).Recently, Jacobsen's team reported that prenatal and teenage exposure to smoke were associated with reduced auditory and visual attention, with boys being particularly vulnerable to auditory deficits. (ciggyfree.com)
  • cigarette
  • Withdrawal symptoms such as cigarette craving can be reduced in most individuals by plasma nicotine levels lower than those from smoking. (drugs.com)
  • Absorption of nicotine through the buccal mucosa is relatively slow and the high and rapid rise followed by the decline in nicotine arterial plasma concentrations seen with cigarette smoking are not achieved with the inhaler. (drugs.com)
  • After use of the single inhaler the arterial nicotine concentrations rise slowly to an average of 6 ng/mL in contrast to those of a cigarette, which increase rapidly and reach a mean C max of approximately 49 ng/mL within 5 minutes. (drugs.com)
  • The time to smoking the first cigarette in the morning is an index of the need for nicotine following an extended, overnight abstinence. (wikipedia.org)
  • inhalation
  • NICOTROL ® Inhaler (nicotine inhalation system) consists of a mouthpiece and a plastic cartridge delivering 4 mg of nicotine from a porous plug containing 10 mg nicotine. (drugs.com)
  • An intensive inhalation regimen (80 deep inhalations over 20 minutes) releases on the average 4 mg of the nicotine content of each cartridge of which about 2 mg is systemically absorbed. (drugs.com)
  • brain
  • Lippiello, P. M. and Fernandes, K. G., 1986, The binding of L[3H]nicotine to a single class of high affinity sites in rat brain membranes, Molec. (springer.com)
  • This is different from the mechanism that regulates nicotine reward and likely occurs in a separate brain area. (innovations-report.com)
  • Brunzell and colleagues are conducting ongoing studies that they hope will help to identify which brain areas regulate the anxiolytic effects of nicotine. (innovations-report.com)
  • Nicotine might cause the teenage brain to develop abnormally, resulting in changes to the structure of white matter - the neural tissue through which signals are relayed. (ciggyfree.com)
  • David McAlpine, director of the Ear Institute at University College London, says the findings are interesting because the key brain pathway affected by nicotine helps determine how we process auditory information when distracted by other tasks. (ciggyfree.com)
  • Once in the brain, it binds to specific nicotine receptors resulting in the release of neurotransmitters, such as dopamine and norepinephrine. (wikipedia.org)
  • With a reduced amount of nicotine reaching the brain, neurotransmitter release is greatly lessened and the pleasurable, positive-reinforcing effects of nicotine are diminished. (wikipedia.org)
  • This illustrates a neuroadaptive response to the lack of nicotine in the system-if the brain needs more nicotine after going all night without any, then the urge to smoke early in the morning will be especially strong. (wikipedia.org)
  • effects
  • Although nicotine (1a), a naturally occurring nAChR ligand, is associated with a variety of toxic side effects, there is no reason to believe that these side effects are inextricably linked to the beneficial effects of nicotinic ligands. (springer.com)
  • One, the "inherent functionality model", assumes that primitive binding pockets are a necessary consequence of protein folding, and that the effects of small molecules on these (probably quite nonspecific) motifs has been honed by evolutionary pressures since then. (sciencemag.org)
  • I'm a medicinal chemist, someone who's used to seeing "magic methyl effects" where very small changes in ligand structure can make big differences in binding to a protein. (sciencemag.org)
  • Both smoking and nicotine can increase circulating cortisol and catecholamines, and tolerance does not develop to the catecholaminereleasing effects of nicotine. (drugs.com)
  • Like many other biologically active substances, acetylcholine exerts its effects by binding to and activating receptors located on the surface of cells. (wikipedia.org)
  • In vitro and in vivo animal studies have shown that homopentameric nAChR inhibitors, such as methyllycaconitine and α-Bgtx, can attenuate nicotine-induced proliferative, angiogenic, and metastatic effects in lung, colon, and bladder cancer cells. (aacrjournals.org)
  • Because the binding of these receptors is unanticipated by the regulated activity of the fetal cells it can be inferred that this is a disruption in the cellular process which can lead to detrimental effects such as the deregulation of vital signaling, expression, or repair. (wikipedia.org)
  • context
  • In this context, nicotine is also plays a proangiogenic role by releasing MMPs, VEGF, and βFGF from ECs and in the tumor microenvironment. (aacrjournals.org)
  • nAChR
  • For cancer therapy, natural compounds such as garcinol and EGCG have been found to block nicotine- and estrogen-induced breast cancer cell proliferation through inhibition of the α9-nAChR signaling pathway. (aacrjournals.org)
  • Cobratoxin binds to the ligand-binding pocket between the α/γ or α/δ nAChR subunits (Chen et al. (wikipedia.org)
  • findings
  • The findings that β-estradiol requires the AGMI sequence but that a single C-terminal tryptophan is sufficient for potentiation by ethynyl β-estradiol indicate that the C terminus forms a binding site for these steroids. (jneurosci.org)
  • block
  • The binding site(s) for block appears to differ from those involved in potentiation because the C-terminal sequence does not affect block by steroids such as progesterone, and progesterone does not competitively inhibit potentiation. (jneurosci.org)
  • activity
  • Barlow RB, Johnson O (1989) Relations between structure and nicotine-like activity: X-ray crystal structure analysis of (-)-cytisine and (-)-lobeline hydrochloride and a comparison with (-)-nicotine and other nicotine-like compounds. (springer.com)
  • Nonetheless, many members of this unplanned family showed real levels of binding to things like heme, and many even showed above-background levels of several types of enzymatic activity. (sciencemag.org)
  • similar
  • And that makes me think that I could probably take a set of binding pockets that Skolnick's people would call so similar as to be basically identical, and still find small molecules that would differentiate them. (sciencemag.org)
  • Neonicotinoids (sometimes shortened to neonics /ˈniːoʊnɪks/) are a class of neuro-active insecticides chemically similar to nicotine. (wikipedia.org)
  • human
  • Mutations indicate that a sequence (AGMI) at the end of the C terminus of the human α4 subunit forms a binding site required for 17β-estradiol potentiation. (jneurosci.org)