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.)
- Jakubík J, Randáková A, Zimčík P, El-Fakahany EE, Doležal V. Binding of N-methylscopolamine to the extracellular domain of muscarinic acetylcholine receptors. Sci Rep. 2017 Jan 16;7:40381.
- 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;97:27-39.
- Michal P, El-Fakahany EE, Doležal V. Changes in membrane cholesterol differentially influence preferential and non-preferential signaling of the M1 and M3 muscarinic acetylcholine receptors. Neurochem Res. 2015;40(10):2068-2077.
- Janickova H, Rudajev V, Dolejsi E, Koivisto H, Jakubik J, Tanila H, El-Fakahany EE, Dolezal V. Lipid-based diets improve muscarinic neurotransmission in the hippocampus of transgenic APPswe/PS1dE9 mice. Curr Alzheimer Res. 2015;12(10):923-31.
- Jakubík J, El-Fakahany EE, Doležal V. Towards predictive docking at aminergic G protein coupled receptors.J Mol Model. 2015;21(11):284.
- 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;86(2):180-192.
- 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.
- Jakubík J, Janíčková H, El-Fakahany EE, Doležal V. Negative cooperativity in binding of muscarinic receptor agonist and GDP as a measure of agonist efficacy. Br J Pharmacol. 2011;162:1029-44.
- Jakubík J, Janíčková H, Randáková A, El-Fakahany EE, Doležal V. Subtype differences in pre-coupling of muscarinic acetylcholine receptors, PLoS ONE 2012;6(11): e27732.
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.