Dr. El-Fakahany collaborates with investigators at the Czech Academy of Science to study the effects and mechanisms of action of drugs that target allosteric binding sites on muscarinic acetylcholine receptors. These include drugs that bind to the receptor in a bimodal fashion, with reversible binding and activation of the primary orthosteric binding domain and irreversible binding and activation at a secondary allosteric site. Binding of drugs at the allosteric site modulates the interaction of agents at the receptor primary site. Allosteric agents are expected to be endowed with significant selectivity for given subtypes of muscarinic acetylcholine receptors.
(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
Randáková A, Dolejší E, Rudajev V, Zimčík P, Doležal V, El-Fakahany EE, Jakubík J. Classical and atypical agonists activate M1 muscarinic acetylcholine receptors through common mechanisms. Pharmacol Res. 2015 Jul;97:27-39.
Michal, P., E. E. El-Fakahany and Dolezal, V. Changes in membrane cholesterol differentially influence preferential and non-preferential signaling of the M1 and M3 muscarinic acetylcholine receptors. Neurochemical Research,40, 2068-2077, 2015.
Janickova, H., V. Rudajev, E. Dolesji, H. Koivisto, J. Jakubik, K. Tanila, E. E. El-Fakahany and V. Dolezal @ . Lipid-based diets improve muscarinic neurotransmission in the hippocampus of transgenic APPswe/PS1dE9 mice. Current Alzheimer Research,12, 923-931, 2015.
Jakubik, J. @ , E.E. El-Fakahany and V. Dolezal. Towards predictive docking at aminergic G protein coupled receptors. J. Molecular Modeling, in press
Jakubík J, Zimčík P, Randáková A, Fuksová K, El-Fakahany EE, Doležal V. Molecular mechanisms of methoctramine binding and selectivity at muscarinic acetylcholine receptors. Mol Pharmacol. 2014 Aug;86(2):180-92.
Šantrůčková E, Doležal V, El-Fakahany EE, Jakubík J. Long-term activation upon brief exposure to xanomleline is unique to M1 and M4 subtypes of muscarinic acetylcholine receptors. PLoS One. 2014 Feb 18;9(2):e88910.
J Jakubík, H Janíčková, EE El-Fakahany and V Doležal. Negative cooperativity in binding of muscarinic receptor agonist and GDP as a measure of agonist efficacy. British Journal of Pharmacology, 162: 1029-1044, 2011. 166.
Jakubik, J., A. Randakova, E.E. El-Fakahany and V. Dolezal. Subtype differences in pre-coupling of muscarinic acetylcholine receptors, PLoS ONE, 6(11): e27732, 2012.
Jakubík, J., A. Randáková, E.E. El-Fakahany and V. Dolezal. Divergence of allosteric effects of rapacuronium on binding and function of muscarinic receptors. BioMed Central Pharmacology, 9 (15), 1-20, 2010. 163.
Jakubik, J. and E.E. El-Fakahany. Allosteric Modulation of Muscarinic Acetylcholine Receptors. Pharmaceuticals, 3, 2838-2860, 2010. 164.
Grant, M.K.O, K. De Lorme, M. Noetzel, J. Jakubik, V. Dolezal and E.E. El-Fakahany. Pharmacological evaluation of the long-term effects of xanomeline on the M1 muscarinic acetylcholine receptor. PLoS ONE, e15722, Dec. 23; 5(12), 2010.
Cabadak, H., A.E. Cuadra, E.E. El-Fakahany and B. Kan. M2, M3 and M4 muscarinic receptors are expressed in the guinea-pig gallbladder. Journal of Receptors and Signal Transduction, 29: 63–66, 2009. 159.
Noetzel, M.J., M.K.O. Grant and E.E. El-Fakahany. Immediate and delayed consequences of xanomeline wash-resistant binding at the M3 muscarinic receptor. Neurochemical Research, 34:1138-1149, 2009 160.
Michal, P., V. Rudajev, E.E. El-Fakahany, V. Doležal..Membrane cholesterol content influences binding properties of muscarinic M2 receptors and differentially impacts activation of second messenger pathways. European Journal of Pharmacology, 606: 50-60, 2009. 161.
Noetzel, M.J., M.K.O. Grant and E.E. El-Fakahany. Mechanisms of M3 muscarinic receptor regulation by wash-resistant xanomeline binding. Pharmacology, 83: 301-317, 2009.
Noetzel MJ, Grant MK, El-Fakahany EE. Immediate and delayed consequences of xanomeline wash-resistant binding at the M3 muscarinic receptor. Neurochem Res. 2009 Jun;34(6):1138-49. Epub 2008 Dec 12.
Kane BE, Grant MK, El-Fakahany EE, Ferguson DM. Synthesis and evaluation of xanomeline analogs--probing the wash-resistant phenomenon at the M1 muscarinic acetylcholine receptor. Bioorg Med Chem. 2008 Feb 1;16(3):1376-92. Epub 2007 Oct 22.
De Lorme KC, Grant MK, Noetzel MJ, Polson SB, El-Fakahany EE. Long-term changes in the muscarinic M1 receptor induced by instantaneous formation of wash-resistant xanomeline-receptor complex. J Pharmacol Exp Ther. 2007 Dec;323(3):868-76.
Kane BE, Grant MK, El-Fakahany EE, Ferguson DM. Synthesis and evaluation of xanomeline analogs-Probing the wash-resistant phenomenon at the M(1) muscarinic acetylcholine receptor. Bioorg Med Chem. 2007 Oct 22.
Machová E, Jakubík J, El-Fakahany EE, Dolezal V. Wash-resistantly bound xanomeline inhibits acetylcholine release by persistent activation of presynaptic M(2) and M(4) muscarinic receptors in rat brain. J Pharmacol Exp Ther. 2007 Jul;322(1):316-23.
Michal P, El-Fakahany EE, Dolezal V. Muscarinic m2 receptors directly activate gq/11 and gs g-proteins. J Pharmacol Exp Ther. 2007 Feb;320(2):607-14.
De Lorme KC, Sikorski KL, Grant MK, El-Fakahany EE. Long-term wash-resistant effects of brief interaction of xanomeline at the M1 muscarinic receptor. Neurosci Lett. 2006 Dec 13;410(1):11-4.
Jakubik J, El-Fakahany EE, Dolezal V. Differences in kinetics of xanomeline binding and selectivity of activation of G proteins at M(1) and M(2) muscarinic acetylcholine receptors. Mol Pharmacol. 2006 Aug;70(2):656-66.
Former Graduate Students
Norman Lee (Ph.D., Pharmacology, Modulation of muscarinic acetylcholine receptors.). Laboratory Director, Institute of Genomic Research, Gaithersburg, MD.
Meredith Noetzel (Ph.D. 2009, Neuroscience, University of Minnesota).
Vickram Ramkumar (Ph.D., Pharmacology; Regulation of neuronal calcium channels). Assistant Professor of Pharmacology, University of Southern Illinois Medical School.