Roger Papke, Ph.D.
We study the physiology, pharmacology, and biophysics of neurotransmitter receptors with a special emphasis on the function of nicotinic acetylcholine receptors in the brain. These are the receptors which mediate the effects of nicotine on human behavior. We study how these neuronal nicotinic acetylcholine receptors function as ligand-gated ion channels, identifying parts of the molecule which are involved with the binding of neurotransmitter and the conformational change associated with receptor activation. We are also characterizing the selectivity of experimental nicotinic agonists for specific receptor subtypes in the brain. With this understanding, we hope to identify the mechanisms through which nicotine-like substances may alleviate some of the learning and memory impairments in animal models of dementia. The ongoing clinical development of new experimental drugs may lead to novel therapeutics for the treatment of Alzheimer’s disease.
- Horenstein NA, Quadri M, Stokes C, Shoaib M, Papke RL. Cracking the Betel Nut: Cholinergic Activity of Areca Alkaloids and Related Compounds. Nicotine Tob Res. 2017 Oct 3. doi: 10.1093/ntr/ntx187.
- Horenstein NA, Papke RL. Anti-inflammatory Silent Agonists. ACS Med Chem Lett. 2017 Sep 26;8(10):989-991. doi: 10.1021/acsmedchemlett.7b00368. eCollection 2017 Oct 12.
- Hueffer K, Khatri S, Rideout S, Harris MB, Papke RL, Stokes C, Schulte MK. Rabies virus modifies host behaviour through a snake-toxin like region of its glycoprotein that inhibits neurotransmitter receptors in the CNS. Sci Rep. 2017 Oct 9;7(1):12818. doi: 10.1038/s41598-017-12726-4.
- Quadri M, Stokes C, Gulsevin A, Felts ACJ, Abboud KA, Papke RL, Horenstein NA. Sulfonium as a Surrogate for Ammonium: A New α7 Nicotinic Acetylcholine Receptor Partial Agonist with Desensitizing Activity. J Med Chem. 2017 Sep 28;60(18):7928-7934. doi: 10.1021/acs.jmedchem.7b00875. Epub 2017 Sep 14.
- Abbas M, Alzarea S, Papke RL, Rahman S. The α7 nicotinic acetylcholine receptor positive allosteric modulator attenuates lipopolysaccharide-induced activation of hippocampal IκB and CD11b gene expression in mice. Drug Discov Ther. 2017;11(4):206-211. doi: 10.5582/ddt.2017.01038.
- Jin Y, Huang X, Papke RL, Jutkiewicz EM, Showalter HD, Zhan CG. Design, synthesis, and biological activity of 5′-phenyl-1,2,5,6-tetrahydro-3,3′-bipyridine analogues as potential antagonists
of nicotinic acetylcholine receptors. Bioorg Med Chem Lett. 2017 Sep 15;27(18):4350-4353. doi: 10.1016/j.bmcl.2017.08.025. Epub 2017 Aug 14.