Cognitive Functions, Attention-Deficit Hyperactivity Disorders, and Alzheimer’s Disease
Divya Vohora in The Third Histamine Receptor, 2008
In addition to the use of aged animals and transgenic mice, Alzheimer’s researchers have long used lesion models to try to reproduce cognitive and cholinergic deficits observed in the human disease. Cholinergic neurons within the basal forebrain nuclei are found alongside various noncholinergic neurons, and nonselective lesions of all neuron types within this area lead to disruptions of cognitive functioning across a number of behavioral tasks including the water maze. In contrast, selective lesions to the basal forebrain cholinergic neurons using the immunotoxin, 192 IgG-saporin, which kills neurons expressing p75 nerve growth factor receptors, does not have much effect on water maze performance in mature rats and has only moderate impairing effects in aged rats [125]. Pharmacological reversal of such lesions has been challenging. For example, the nicotinic agonist, ABT-418, failed to improve measures of sustained attention in a rat-operant task in 192 IgG-saporin-lesioned rats, whereas it readily improved performance in sham-operated rats [126].
Pyrantel and Oxantel Pamoate
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
A single report of pyrantel treatment failure against Ancylostoma duodenale exists (Reynoldson et al., 1997). This community-based study found that administration of pyrantel as a single 10 mg/kg dose to individuals naturally infected with A. duodenale had little effect on estimated hookworm burdens. The validity of these results have been questioned due to the omission of an untreated control group and the lack of attempted in vitro confirmation (Geerts and Gryseels, 2000). Hence there is no conclusive evidence that any of the human-infecting nematode species targeted by pyrantel have developed resistance to this drug. In spite of this, it is worth noting that resistance to pyrantel has been well documented in nematodes infecting domestic animal species—namely, pigs (Roepstorff et al., 1987), horses (Drudge et al., 1988), and canines (Kopp et al., 2007a). The mechanism of resistance to anthelmintics that act as nicotinic agonist drugs, including pyrantel, levamisole, morantel, and oxantel, remains poorly understood (Wolstenholme et al., 2004).
Stimulus-Secretion Coupling: Intracellular Proteins and Nucleotides
Stephen W. Carmichael, Susan L. Stoddard in The Adrenal Medulla 1986 - 1988, 2017
TerBush, Bittner, and Holz (1988) investigated protein kinase C translocation from cytosol to membrane in response to a nicotinic agonist and to depolarization with high potassium concentration. The significant and unique aspects of their study included: 1) the demonstration that calcium ion influx causes an extremely rapid (within 2 seconds) translocation of protein kinase C to membranes which correlate well with the secretory response; and 2) the development of a method to quantitate the relationship between membrane-bound protein kinase C and the enhancement of calcium-dependent secretion. This quantitation leads to the conclusion that secretagogue-induced translocation of protein kinase C to membranes is sufficient to enhance the secretory response.
(E)-3-furan-2-yl-N-phenylacrylamide (PAM-4) decreases nociception and emotional manifestations of neuropathic pain in mice by α7 nicotinic acetylcholine receptor potentiation
Published in Neurological Research, 2021
Deniz Bagdas, Gulce Sevdar, Zulfiye Gul, Rabha Younis, Sinan Cavun, Han-Shen Tae, Marcelo O. Ortells, Hugo R. Arias, Mine Sibel Gurun
Further, epidemiological and clinical studies show that there is an interaction between chronic pain and tobacco use as seen in increased prevalence of tobacco use among chronic pain patients [6–10]. The reason behind being pain as a potent motivator of tobacco use can be explained in two ways: either nicotine, main ingredient in tobacco, can reduce pain or pain-related affective signs, such as depression and anxiety, increase nicotine use motivation [10–13]. A recent paper revealed that there is a correlation between nicotine dependence and the sensitivity and severity of anxiety status induced by chronic pain [13]. Indeed, previous preclinical studies show that nicotine is able to reduce both sensorial [14,15] and affective signs [15] of pain. Therefore, nicotine is a promising agent, acting as a prototypical nicotinic agonist. These dual effects of nicotine open new windows of opportunity in the use of nicotinic analogs with less side effects for pain management.
Cell signal transduction: hormones, neurotransmitters and therapeutic drugs relate to purine nucleotide structure
Published in Journal of Receptors and Signal Transduction, 2018
W. R. Williams
Adjacent atoms in the guanine ring provide fitting points for low molecular weight amino acid transmitters operating at LGIC in Figure 5. Glutamate and co-agonist glycine structures together superimpose on a large area of the GTP template [1] with fitting points common to NMDA [2], quinolinic acid [3], kainate [5] and AMPA [7]. Agonist and antagonist [4,6,8] structures use the same fitting points. 5-HT3 receptor agonists [9–11] fit to the imidazole moiety of the guanine ring, in contrast to the antagonist structure of ondansetron that superimposes across the guanine ring. NMDA, 5-HT, acetylcholine [13] and GABA [20] structures make use of C4 and C5 fitting points. 5-HT3 receptors are especially abundant in GABAergic inter-neurons in cortical and hippocampal regions of the brain, and co-localize with and cross-regulate GABAA and nicotinic receptors [25,26]. The fit of acetylcholine structures [13,14] to adjacent carbons either side of N9 on the GTP template is replicated by nicotine, PTMA [15,16] and anatoxin-a [17]. Nicotinic agonist and antagonist structures [18,19] differ significantly in regard to their relationship to the GTP template. The N9C4C5 nicotine fit of acetylcholine is also replicated by the structures of carbamoylcholine, RJR2429 and SIB1508Y (data not shown).
An overview on cyanobacterial blooms and toxins production: their occurrence and influencing factors
Published in Toxin Reviews, 2022
Isaac Yaw Massey, Muwaffak Al osman, Fei Yang
Anatoxin-a is a small alkaloid and potent neurotoxin promoter. It is a bicylic secondary amine, smallest cyanotoxin, and has a molecular weight of 165 Da. Osswald et al. (2007) indicated that Anabaena sp., Aphanizomenon sp., Microcystis sp., Oscillatoria sp., Arthrospira sp., Raphidiopsis sp., Planktothrix sp., Phormidium sp., Nostoc sp. and Cylindrospermum sp. are capable to produce this toxin. The amine pKa value of 9.4 renders the cationic form of anatoxin-a the most prevalent form in natural waters and its oxidation may be pH-dependent. Homoanatoxin-a with an additional methylene unit on its side chain has been identified as a variant of anatoxin-a (Skulberg et al.1992). Anatoxin-a is a potent nicotinic agonist capable of producing neuromuscular blockade leading to paralysis and eventually death owing to respiratory arrest (Fawell et al.1999, Osswald et al.2007). Although anatoxin-a is not considered widespread as the cyclic peptide hepatotoxins, it is documented to have caused animal poisonings in some parts of the world identified (Fawell et al.1993, Sivonen and Jones 1999, Svircev et al.2019). Due to the toxic consequences, Fawell et al. (1999) recommended 1 µg/L anatoxin-a concentration to provide significant water safety since no official drinking water guideline is established.