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Visualization of Cholinergic Tracers in Alzheimer Brains in vivo by Positron Emission Tomography
Published in Robert E. Becker, Ezio Giacobini, Alzheimer Disease, 2020
Agneta Nordberg, Per Hartvig, Hans Lundqvist, Andres Lilja, Matti Viitanen, Kaarina Amberla, J. Ulin, Bengt Winbald, Bengt Bengt Långström
Higher uptake of (+) and especially (-) 11C-nicotine to brain has been observed in young smokers compared age-matched non-smokers (Nybäck et al. 1989). The observation agrees with findings of an enhanched number of high affinity nicotinic receptors in postmortem brains of smokers (Benwell et al. 1988) and nicotinic receptor increase in animals following nicotine treatment (Romanelli et al. 1988).
Treatment Of Alzheimer’s Disease
Published in Zaven S. Khachaturian, Teresa S. Radebaugh, Alzheimer’s Disease, 2019
Lina Shihabuddin, Kenneth L. Davis
Other drugs which are partial Ml agonists and partial M2 antagonists which might alleviate central cholinergic deficits in Alzheimer’s disease with less peripheral side effects are under development. Since the deficits in Alzheimer’s disease involve both the muscarinic and the nicotinic system, agents that stimulate the nicotinic receptors as well are worth consideration.
Medical Management of Chemical Warfare Agents
Published in Brian J. Lukey, James A. Romano, Salem Harry, Chemical Warfare Agents, 2019
Another toxidrome is the cholinergic toxidrome, also known as nerve agents. This is caused by organophosphates and carbamates, which are commonly used in pesticides and thus, another common substance in our society. Related organophosphates are in nerve agents. These substances bind to, and thus disable the functioning of, acetylcholinesterase. Acetylcholinesterase turns off nerve impulses at the synaptic junction once acetylcholine neurotransmitters have delivered their messages. Its inhibition leaves these nerve circuits fully switched on. The symptoms derive from the progressive turned-on state of these nerves. The major difference between the two is that organophosphates bind irreversibly, while the carbamates bind reversibly. Both muscarinic and nicotinic receptors are affected. However, you will find both features present in the cholinergic toxidrome. During the middle period, there can be alteration, as both sympathethic and parasympathetic try to predominate.
Anticholinergics and falls in older adults
Published in Expert Review of Clinical Pharmacology, 2022
Acetylcholine is a neurotransmitter synthesized from choline and acetyl-CoA during catalysis of choline acetyltransferase [36], and produces nerve signaling by binding to nicotinic and muscarinic receptors on the postsynaptic membrane of neurons. Muscarinic receptors are abundant in the effector cells innervated by the post-ganglionic fibers of parasympathetic nerves [37]. Receptor binding leads to excitation of parasympathetic nerve endings [38], leading to the inhibition of heart activity and bronchial smooth muscles, smooth muscles of the gastrointestinal tract, contraction of the bladder and pupillary sphincters, and increased secretion of digestive glands [39]. Nicotinic receptors are found in the postsynaptic membranes of sympathetic and parasympathetic neurons and the terminal membranes of neuromuscular junctions [40,41]. Excitation of post-ganglionic neurons through nicotinic acetylcholine receptor binding then leads to activation of skeletal muscles.
Spider toxins targeting ligand-gated ion channels
Published in Toxin Reviews, 2021
Compared to glutamatergic receptors, nicotinic receptors are not exploited by spider toxins to the fullest capacity. Despite this, there are several toxins that target nicotinic receptors. Some of them possess polyamine structure (JSTX-3, VdTx-I), others are peptidic (ω-agatoxin IVA, κ-hexatoxin-Hv1c). The functionality of these toxins was shown in several in vitro preparations where nicotinic receptors are involved. Thorough investigation of details of molecular interaction is missing, however. Most of the characterized spider toxins acting on nicotinic receptors act as inhibitors (JSTX-3, VdTx-I, and ω-agatoxin IVA). One (κ-hexatoxin-Hv1c) acts as a positive allosteric modulator. The details of toxin–receptor interaction for all aforementioned toxins are worth investigation as far as they can yield useful information for rational drug design.
Therapeutic approaches to cholinergic deficiency in Lewy body diseases
Published in Expert Review of Neurotherapeutics, 2020
Matthew J. Barrett, Leslie J. Cloud, Harsh Shah, Kathryn L. Holloway
In contrast to the overall increased cortical densities of muscarinic receptors observed in Lewy body diseases, pathological studies show reduced nicotinic receptors in cortex and hippocampus in PD [102–104]. In one of these studies, reduction in frontal cortex nicotinic receptors correlated with the severity of dementia [103]. Reductions in both α7 and non-α7 nicotinic receptors were also found in DLB. Interestingly, only the reduction in α7 receptors was correlated with cholinergic denervation as measured by choline acetyltransferase activity [105]. Another study found that reduction in α7 nicotinic receptors in the temporal cortex was associated with visual hallucinations and delusional misidentification in DLB [106]. Similar to pathological studies, nuclear imaging studies in PD using radioligands selective for α4β2* nicotinic receptors demonstrate widespread reduction in cortical and subcortical receptor densities [107,108]. In DLB, a SPECT study using the α4β2* nicotinic receptor ligand 5-[123I]-A-85380 showed reduced binding in frontal and cingulate regions corresponding to worse executive dysfunction [109]. Reduced striatal and substantia nigral binding of 5-[123I]-A-85380 is also a feature of DLB and PD and is thought to reflect presynaptic dopaminergic neuronal degeneration [110].