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Plant-Based Secondary Metabolites for Health Benefits
Published in Hafiz Ansar Rasul Suleria, Megh R. Goyal, Masood Sadiq Butt, Phytochemicals from Medicinal Plants, 2019
Monika Sharma, Jyotsana Dwivedi, Bhanu Kumar, Bramhanand Singh, A. K. S. Rawat
Research has unveiled that animals are also a source of some interesting novel drugs. Venoms and toxins from animal sources are in use for curing various diseases. Epibatidine is 200-folds more effective in comparison with morphine and it is extracted from Ecuadorian poison frog skin. Teprotide is obtained from a Brazilian viper that has been used for developing hypertension drugs cilazapril and captopril.67,68
ENTRIES A–Z
Published in Philip Winn, Dictionary of Biological Psychology, 2003
Many South and Central American frogs—typically tiny (around 2 cm long) and vividly coloured—have poisons in their SKIN, typically present over all the skin rather than in localized patches. The poisons serve to protect the frogs (as SPECIES) from predation. The skin of many frogs and toads contain chemicals that can cause HALLUCINATIONS, but the skin of poison dart frogs (of which there are many different species) contains a poison that can cause CONVULSIONS, PARALYSIS and eventually death (which is why native peoples have used the skin poisons, carefully collected, to tip darts and arrows used for hunting). The poison is an alkaloid, EPIBATIDINE, which the frogs synthesize from dietary components (see ALKALOIDS). Laboratory analysis has shown that it has an action at NICOTINIC ACETYLCHOLINE RECEPTORS and is a potent analgesic. While epibatidine itself cannot be used therapeutically, derivatives appear likely to be useful analgesic agents.
Synthesis, Enzyme Localization, and Regulation of Neurosteroids
Published in Sheryl S. Smith, Neurosteroid Effects in the Central Nervous System, 2003
Evers, A.S., Enantioselectivity of pregnanolone-induced gamma-aminobutyric acid(A) receptor modulation and anesthesia, J. Pharmacol. Exp. Ther., 293, 1009-1016, 2000. Zhang, X. and Nordberg, A., The competition of (-)-[3H]nicotine binding by the enantiomers of nicotine, nornicotine and anatoxin-a in membranes and solubilized preparations of different brain regions of rat, Naunyn Schmiedebergs Arch. Pharmacol., 348, 28-34, 1993.Badio, B. and Daly, J.W., Epibatidine, a potent analgetic and nicotinic agonist, Mol. Pharmacol., 45, 563-569, 1994.Abreo, M.A., Lin, N.H., Garvey, D.S., Gunn, D.E., Hettinger, A.M., Wasicak, J.T., Pavlik, P.A., Martin, Y.C., Donnellγ-Roberts, D.L., Anderson, D.J., Sullivan, J.P., Williams, M., Arneric, S.P., and Holladay, M.W., Novel 3-pyridyl ethers with subna-nomolar affinity for central neuronal nicotinic acetylcholine receptors, J. Med. Chem., 39, 817-825, 1996.Demirgoren, S., Majewska, M.D., Spivak, C.E., and London, E.D., Receptor binding and electrophysiological effects of dehydroepiandrosterone sulfate, an antagonist of the GABAA receptor, Neuroscience, 45, 127-135, 1991.Majewska, M.D., Demirgoren, S., Spivak, C.E., and London, E.D., The neurosteroid dehydroepiandrosterone sulfate is an allosteric antagonist of the GABAA receptor, Brain Res., 526, 143-146, 1990.Nilsson, K.R., Zorumski, C.F., and Covey, D.F., Neurosteroid analogues. 6. The synthesis and GABAA receptor pharmacology of enantiomers of dehydroepiandrosterone sulfate, pregnenolone sulfate, and (3-alpha,5-beta)-3-hydroxypregnan-20-one sulfate, J. Med. Chem., 41, 2604-2613, 1998.Weaver, C.E., Jr., Marek, P., Park-Chung, M., Tam, S.W., and Farb, D.H., Neuropro-
The piperazine scaffold for novel drug discovery efforts: the evidence to date
Published in Expert Opinion on Drug Discovery, 2022
Maria Novella Romanelli, Dina Manetti, Laura Braconi, Silvia Dei, Alessio Gabellini, Elisabetta Teodori
An important motivation for inserting those bicyclic structures can be related to the discovery of epibatidine (40), an alkaloid found in the skin extracts from the Ecuadorian poison frog Epipedobates tricolor [65], exhibiting high potency on several nAChR receptor subtypes [66]. The remarkable analgesic activity of this compound stimulated the synthesis of a high number of analogues deriving from replacement of the 7-azabicyclo[2.2.1]heptane ring, with the aim of obtaining potent subtype selective compounds. Epibatidine has an exo configuration; epimerization of the stereogenic center in position 2 gave the endo isomer endowed with much lower activity. The critical stereogenic center could be eliminated by substituting the bicyclic moiety with diazabicycloalkanes and using the second N atom as attachment point for the aromatic heterocycle. Toward this aim, the bicyclic moiety of epibatidine has been replaced with 2,5-DBO, 2,5-DBH, 3,6-DBH, and 3,8-DBO (compounds 41–44, Figure 6). 2,5-DBH is a rigid moiety carrying the piperazine ring locked into a twisted boat geometry; theoretical calculations predicted that in 3,6-DBH and 3,8-DBO, the piperazine ring could assume a boat or chair conformation, with the latter being energetically favored [64,67].
Cell signal transduction: hormones, neurotransmitters and therapeutic drugs relate to purine nucleotide structure
Published in Journal of Receptors and Signal Transduction, 2018
Molecular structure has a direct bearing on ligand specificity in regard to the interaction of purine nucleotides and G-proteins with cell membrane receptors. Equilibrium binding studies on the M2 acetylcholine receptor demonstrate that depletion of membrane-bound GDP increases the proportion of high-affinity agonist sites, and carbachol accelerates the dissociation of GDP [14]. The binding of α7 nicotinic acetylcholine receptors to Gα and Gβγ proteins decreases in the presence of ligand [15]. Some commonality in the functional properties of receptor ligands extends across receptor classes. Antiarrhythmics, anesthetics, antidepressants, histamine (H1) and calcium channel antagonists all block the glibenclamide sensitive K+ current [16]. Nicotinic ligands such as epibatidine and tubocurarine bind with high potency to a serotonin (5-HT3) receptor and serotonin acts as a nicotinic antagonist [17]. The therapeutic consequences of poor drug-receptor specificity are evident in the concepts of pharmacological promiscuity and network pharmacology [18,19].
Quercetin promotes gastrointestinal motility and mucin secretion in loperamide-induced constipation of SD rats through regulation of the mAChRs downstream signal
Published in Pharmaceutical Biology, 2018
Ji Eun Kim, Mi Rim Lee, Jin Ju Park, Jun Young Choi, Bo Ram Song, Hong Joo Son, Young Whan Choi, Kyung Mi Kim, Jin Tae Hong, Dae Youn Hwang
Finally, the mAChRs mediate the actions of the neurotransmitter (ACh) in the central nerve system (CNS), peripheral nervous system (PNS) and the end organs of the parasympathetic nerves (van Koppena and Kaiser 2003; Ishii and Kurachi 2006). These receptors stimulate signal transduction pathways through the interactions with G protein, although five subtypes (M1–M5) were coupled with toxin-insensitive and toxin-sensitive G subtype protein (Caulfield 1993; Rümenapp et al. 2001). Furthermore, numerous compounds bind to the mAChRs as agonist including acetylcholine, nicotine, muscarine and epibatidine, as well as antagonist including atropine, pirenzepine and methoctramine (Ehlert et al. 2012). Two flavonoids, ombuin and QCT, possess high binding affinity to mAChR M1 (Ki = 40–110 µM) (Swaminathan et al. 2014). However, there are no reports on the interaction between QCT and mAChR during the improvement of constipation. In the present study, the mAChR expression and downstream signalling pathway dramatically recovered after the QCT treatment. Also, the stimulation of QCT was significantly prevented by the antagonist of mAChR in pRISMCs, as shown in Figure 6. These results therefore provide scientific evidence that the binding between QCT and mAChR plays a key role during the improvement of constipation induced with Lop injection. However, the current study regarding the inhibitory effects of mAChR antogonists (ATR) have some limitations and restrictions, for a clinical application of the results obtained from in vitro conditions to in vivo conditions.