Department of Pharmacology and Experimental Therapeutics

William S. Messer, Ph.D.

Photo of Dr. Bill Messer

VP of Research, The University of Toledo

Professor 
Department of Pharmacology and Experimental Therapeutics
419.383.1958 Phone
419.383.1909 FAX
Frederic and Mary Wolfe Center, 274C
wmesser@utnet.utoledo.edu

Education

B.S.     Springfield College
Biology
M.S.     University of Rochester
Neuroscience
Ph.D.     University of Rochester
Neuroscience

 Research Interests 

  • Development of new treatments for neurological disorders
  • Synthesis and pharmacological characterization of novel M1 agonists for Alzheimer's disease
  • Synthesis and biological evaluation of M4 agonists for schizophrenia
  • Development of selective M5 antagonists for the treatment of drug abuse
  • Application of pharmacogenomic principles to the treatment of depression

Recent Publications

Messer, W.S., Jr., B.R. Ellerbrock, D.A. Smith and W. Hoss.  Regional differences in the binding of selective muscarinic antagonists to rat brain:  Comparison with minimum energy conformations.  J. Med. Chem. 32:  1164-1172, 1989. 

Hoss, W., W.S. Messer, Jr., F.J. Monsma, Jr., M.D. Miller, B.R. Ellerbrock, T. Scranton, S. Ghodsi-Hovsepian, M.A. Price, S. Balan, Z. Mazloum and M. Bohnett.  Biochemical and behavioral evidence for muscarinic autoreceptors in the CNS.  Brain Res.  517:  195-201, 1990.   

Messer, W.S., Jr., M. Bohnett and J. Stibbe.  Evidence for a preferential involvement of M1 muscarinic receptors in representational memory.  Neurosci. Lett.  116:  184-189, 1990. 

Messer, W.S., Jr., J.R. Stibbe and M. Bohnett.  Involvement of the septohippocampal cholinergic system in representational memory.  Brain Res.  564:  66-72, 1991. 

Dunbar, P.G., G.J. Durant, Z. Fang, Y.F. Abuh, A. El-Assadi, D.O. Ngur, S. Periyasamy, W. Hoss, and W.S. Messer, Jr.  Design, synthesis, and neurochemical evaluation of 5-(3-alkyl-1,2,4-oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidines as M1 muscarinic receptor agonists.  J. Med. Chem.  36:  842-847, 1993. 

Messer, W.S., Jr., Y.F. Abuh, Y. Liu, S. Periyasamy, D.O. Ngur, M.A.N. Edgar, A.A. El-Assadi, S. Sbeih, P.G. Dunbar, S. Roknich, T. Rho, Z. Fang, B. Ojo, H. Zhang, J.J. Huzl, III, and P.I. Nagy.  Synthesis and biological characterization of 1,4,5,6-tetrahydropyrimidine and 2-amino-3,4,5,6-tetrahydropyrimidine derivatives as selective m1 agonists.  J. Med. Chem.  40:  1230-1246, 1997.

Messer, W.S., Jr., Y.F. Abuh, K. Ryan, M.A. Shepherd, M. Schroeder, S. Abunada and A.A. El-Assadi.  Tetrahydropyrimidine derivatives display functional selectivity for M1 muscarinic receptors in brain.  Drug Dev. Res.  40:  171-174, 1997.

Huang, X.-P., S. Peseckis, F. Williams, and W.S. Messer, Jr.  Pharmacological characterization of human m1 muscarinic acetylcholine receptors with double mutations at the junction of TM VI and the third extracellular domain. J. Pharmacol. Exp. Therap. 286(3): 1129-39, 1998.

Huang, X.-P., P.I. Nagy, F.E. Williams, S.M. Peseckis, and W.S. Messer, Jr.  Role of threonine 192 and asparagine 382 in agonist and antagonist interactions with m1 muscarinic receptors.  Br. J. Pharmacol, 126(3): 735-45, 1999.

Huang, X.-P., F.E. Williams, S.M. Peseckis, and W.S. Messer, Jr. Differential modulation of agonist potency and receptor coupling by mutations of Ser388Tyr and Thr389Pro at the junction of transmembrane domain VI and the third extracellular loop of human M1 muscarinic acetylcholine receptors. Mol. Pharmacol. 56:  775-783, 1999.

Rajeswaran, W.G., Y. Cao, X.-P. Huang, M.E. Wroblewski, T. Colclough, S. Lee, F. Liu, P.I. Nagy, J. Ellis, B.A. Levine, K.H. Nocka and W.S. Messer, Jr.  Design, synthesis and biological characterization of bivalent 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as selective muscarinic agonists. J. Med. Chem.  44(26): 4563-4576, 2001.

Messer, W.S., Jr., K.A. Bachmann, C. Dockery, A.A. El-Assadi, E. Hassoun, N. Haupt, B. Tang and X. Li.  Development of CDD-0102 as a selective M1 agonist for the treatment of Alzheimer’s disease.  Drug Dev. Res.  57(4): 200-213, 2002.

Cao, Y., M. Zhang, C. Wu, S. Lee, M.E. Wroblewski, T. Whipple, P.I. Nagy, K. Takács-Novák, A. Balázs, S. Tőrös and William S. Messer, Jr.  Synthesis and biological characterization of 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as muscarinic agonists for the treatment of neurological disorders. J. Med. Chem.  46: 4273-4286, 2003.

Messer, W.S., Jr., Bivalent ligands for G protein-coupled receptors, Curr. Pharm. Des. 10: 2015-2020, 2004.

Tejada, F., P.I. Nagy, M. Xu, T. Katz, J. Dorsey, M. Rieman, E. Lawlor and W.S. Messer, Jr., Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol) (3-methoxy-1,2,5-thiadiazol-4-yl)[3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-l]ether (CDD-0304): effects of varying the spacer on the binding and activity at muscarinic receptor subtypes. J. Med. Chem. 49(25):  7518-7531, 2006.

 Turvin, J.C., W.S. Messer, Jr. and M.F. Kritzer.  On again, off again effects of gonadectomy on the acoustic startle reflex in adult male rats. Physiol. Behav. 90(2-3): 473-82, 2007.

Rajeswaran, W.G., Y. Cao, X.-P. Huang, M.E. Wroblewski, T. Colclough, S. Lee, F. Liu, P.I. Nagy, J. Ellis, B.A. Levine, K.H. Nocka and W.S. Messer, Jr. Design, synthesis and biological characterization of bivalent 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as selective muscarinic agonists. J. Med. Chem. 44(26): 4563-4576, 2001.

Messer, W.S., Jr., Cholinergic agonists and the treatment of Alzheimer's disease. Curr. Top. Med. Chem. 2(4): 353-358, 2002.

Williams, F.E., D. White and W.S. Messer, Jr. A simple spatial alternation task for assessing memory function in zebrafish. Behav. Proc. 58: 125-132, 2002.

Messer, W.S., Jr., The utility of muscarinic agonists in the treatment of Alzheimer�s disease. J. Mol. Neurosci. 19: 187-193, 2002.

Wise, D.D., T.V. Barkhimer, P.-A. Brault, J.R. Kirchhoff, W.S. Messer, Jr. and R.A. Hudson. Internal standard method for the measurement of choline and acetylcholine by capillary electrophoresis with electrochemical detection. J. Chromatogr. B Biomed. Sci. Appl. 775(1): 49-56, 2002.

Huang, X., H. Xiao, E.B. Rex, R.J. Hobson, W.S. Messer, P.R. Komuniecki and R.W. Komuniecki. Functional characterization of alternatively spliced 5-HT2 receptor isoforms from the pharynx and muscle of the parasitic nematode, Ascaris suum. J. Neurochem. 83: 249-258, 2002.

Barkhimer, T., J.R. Kirchhoff, R.A. Hudson and W.S. Messer, Jr. Evaluation of the inhibition of choline uptake in synaptosomes by capillary electrophoresis with electrochemical detection. Electrophoresis 23(21): 3699-704, 2002.

Messer, W.S., Jr., K.A. Bachmann, C. Dockery, A.A. El-Assadi, E. Hassoun, N. Haupt, B. Tang and X. Li. Development of CDD-0102 as a selective M1 agonist for the treatment of Alzheimer's disease. Drug Dev. Res. 57(4): 200-213, 2002.

Cao, Y., M. Zhang, C. Wu, S. Lee, M.E. Wroblewski, T. Whipple, P.I. Nagy, K. Takcs-Novk, A. Balzs, S. Tors and William S. Messer, Jr. Synthesis and biological characterization of 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as muscarinic agonists for the treatment of neurological disorders. J. Med. Chem. 46: 4273-4286, 2003.

Messer, W.S., Jr., Drugs that target muscarinic cholinergic receptors, in Cognitive Enhancing Drugs, edited by J. Buccafusco, Birkh�user Verlag, pp. 37-48, 2004.

Williams, F.E. and W.S. Messer, Jr. Muscarinic acetylcholine receptors in the brain of zebrafish (Danio rerio) measured by radioligand binding techniques. Comp. Biochem. Physiol. 137(4): 349-353, 2004.

Messer, W.S., Jr., Bivalent ligands for G protein-coupled receptors, Curr. Pharm. Des., 10: 2015-2020, 2004.

Nagy, P.I., F. Tejada and W.S. Messer, Jr. Conformational analysis and derivation of molecular mechanics parameters for esters and thioesters. J. Phys. Chem. (in press).

Nagy, P.I., A. Maheshwari, Y.-W. Kim and W.S. Messer, Jr.  Theoretical and experimental studies of the isomeric protonation in solution for a prototype aliphatic ring containing two nitrogens.  J. Phys. Chem. B. 114(1):  349–360, 2010.

Nagy, P.I. and W.S. Messer, Jr.  Theoretical studies of the in solution isomeric protonation of non-aromatic six-member rings with two nitrogens.  J. Phys. Chem. B., 115:  4758–4767, 2011.

Dokas, L.A, A.M. Malone, F.E. Williams, S.M. Nauli and W.S. Messer, Jr.  Multiple protein kinases determine the phosphorylated state of the small heat shock protein, HSP27, in SH-SY5Y neuroblastoma cells. Neuropharmacol. 61(1-2):  12-24, 2011.

Nagy, P.I., F.R. Tejada, Y.-W. Kim and W.S. Messer, Jr. Theoretical studies of the solvent effect on conformational equilibria and atomic charges for isolated and hydrogen-bonded dimethoxy thiadiazoles. Comp. Theor. Chem. 966:  194-206, 2011.

Ragozzino, M.E., S. Artis, A. Singh, T.M. Twose, J.E. Beck and W.S. Messer, Jr.  The selective M1 muscarinic cholinergic agonist CDD-0102A enhances working memory and cognitive flexibility.  J. Pharmacol. Exp. Therap.  340:  588-594, 2012.

Last Updated: 3/22/15