William S Messer
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Professor of Pharmacology
Professor of Medicinal Chemistry, Pharmacology , College of Pharmacy and Pharmaceutical Sciences
Contact Info
Overview
overview
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Biography – William S. Messer, Jr.
Dr. Messer grew up in western Massachusetts and received a BS in Biology from Springfield College and an MS and PhD in Neuroscience from the University of Rochester. He joined the faculty of the College of Pharmacy at the University of Toledo in 1985 as an assistant professor in the Department of Medicinal & Biological Chemistry. He was promoted to professor of medicinal chemistry in 1995 and then professor of pharmacology in 2001. Dr. Messer served as Chair of the Department of Pharmacology from 2001-2013, and as Vice President of Research at the University of Toledo from 2013-2016 before rejoining the College of Pharmacy and Pharmaceutical Sciences as a full-time faculty member.
Dr. Messer’s research interests have focused on the development of new treatments for neurological and psychiatric disorders, including Alzheimer’s disease, schizophrenia, and autism spectrum disorders. He led a team of investigators that developed a selective M1 muscarinic agonist, CDD-0102A, as a potential treatment for memory and cognitive deficits associated with Alzheimer’s disease. He co-founded a small pharmaceutical company (Cognitive Pharmaceuticals Ltd.) and helped compile the necessary preclinical data for filing a successful IND with the FDA. Following the merger of Cognitive with Mithridion, Inc., he served as Chief Scientific Officer as CDD-0102A was evaluated in Phase I clinical trials.
Since returning to a full-time faculty position, Dr. Messer has focused on teaching pharmacy students and developing novel allosteric modulators of muscarinic receptors. He also founded a new company, Psyneurgy Pharmaceuticals LLC, to develop new treatments for autism spectrum disorders and other psychiatric and neurological disorders.
Publications
selected publications
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Article (Faculty180)
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2024Muscarinic receptor activation promotes destabilization and updating of object location memories in mice. Behavioural brain research. 461:114847.
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2022Effects of the Partial M1 Muscarinic Cholinergic Receptor Agonist CDD-0102A on Stereotyped Motor Behaviors and Reversal Learning in the BTBR Mouse Model of Autism. The international journal of neuropsychopharmacology. 25:64-74.
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2014Evaluation of 1,2,5-thiadiazoles as modulators of M₁/M₅ muscarinic receptor subtypes. Bioorganic & medicinal chemistry. 22:1838-44.
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2011Theoretical studies of the in-solution isomeric protonation of non-aromatic six-member rings with two nitrogens. The journal of physical chemistry. B. 115:4758-67.
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2010Theoretical and experimental studies of the isomeric protonation in solution for a prototype aliphatic ring containing two nitrogens. The journal of physical chemistry. B. 114:349-60.
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2007On again, off again effects of gonadectomy on the acoustic startle reflex in adult male rats. Physiology & behavior. 90:473-82.
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2005Theoretical studies of the tautomeric equilibria for five-member N-heterocycles in the gas phase and in solution. The journal of physical chemistry. B. 109:22588-602.
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2004Muscarinic acetylcholine receptors in the brain of the zebrafish (Danio rerio) measured by radioligand binding techniques. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP. 137:349-53.
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2002A simple spatial alternation task for assessing memory function in zebrafish. Behavioural processes. 58:125-132.
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2002Evaluation of the inhibition of choline uptake in synaptosomes by capillary electrophoresis with electrochemical detection. Electrophoresis. 23:3699-704.
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2002Functional characterization of alternatively spliced 5-HT2 receptor isoforms from the pharynx and muscle of the parasitic nematode, Ascaris suum. Journal of neurochemistry. 83:249-58.
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2002Internal standard method for the measurement of choline and acetylcholine by capillary electrophoresis with electrochemical detection. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. 775:49-56.
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2002The utility of muscarinic agonists in the treatment of Alzheimer's disease. Journal of molecular neuroscience : MN. 19:187-93.
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1999First fatty acylated dipeptides to affect muscarinic receptor ligand binding. Bioorganic & medicinal chemistry letters. 9:3363-8.
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1997Synthesis and biological characterization of 1,4,5,6-tetrahydropyrimidine and 2-amino-3,4,5,6-tetrahydropyridine derivatives as selective m1 agonists. Journal of medicinal chemistry. 40:1230-46.
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1996Heart and T-lymphocyte cell surfaces both exhibit positive cooperativity in binding a membrane-lytic toxin. The Journal of membrane biology. 150:113-22.
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1993Design, synthesis, and neurochemical evaluation of 5-(3-alkyl-1,2,4- oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidines as M1 muscarinic receptor agonists. Journal of medicinal chemistry. 36:842-7.
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1993Inhibition and inactivation of presynaptic cholinergic markers using redox-reactive choline analogs. Journal of medicinal chemistry. 36:1893-901.
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1993
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1992
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1992Steric and electronic requirements for muscarinic receptor-stimulated phosphoinositide turnover in the CNS in a series of arecoline bioisosteres. Biochemical and biophysical research communications. 187:1389-94.
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1991Regulation of muscarinic receptors by intrahippocampal injections of gallamine. Brain research. 564:73-8.
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1990Biochemical and behavioral evidence for muscarinic autoreceptors in the CNS. Brain research. 517:195-201.
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1990Differential coupling between muscarinic receptors and G-proteins in regions of the rat brain. Biochemical pharmacology. 39:1385-91.
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1990Evidence for a preferential involvement of M1 muscarinic receptors in representational memory. Neuroscience letters. 116:184-9.
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1990Subtype specificity of the muscarinic receptor-stimulated GTPase response in the rat cortex. Neuroscience letters. 110:148-54.
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1989Autoradiographic analyses of agonist binding to muscarinic receptor subtypes. Biochemical pharmacology. 38:837-50.
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1989Interaction of amitriptyline with muscarinic receptor subtypes in the rat brain. Neurochemistry international. 14:447-54.
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Article (Web of Science)
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2022Effects of the Partial M-1 Muscarinic Cholinergic Receptor Agonist CDD-0102A on Stereotyped Motor Behaviors and Reversal Learning in the BTBR Mouse Model of Autism. INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY. 25:64-74.Full Text via DOI: 10.1093/ijnp/pyab079 PMID: 34791301
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2017Linking muscarinic receptor activation to UPS-mediated object memory destabilization: Implications for long-term memory modification and storage. NEUROBIOLOGY OF LEARNING AND MEMORY. 145:151-164.Full Text via DOI: 10.1016/j.nlm.2017.10.007
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2014Evaluation of 1,2,5-thiadiazoles as modulators of M-1/M-5 muscarinic receptor subtypes. BIOORGANIC & MEDICINAL CHEMISTRY. 22:1838-1844.Full Text via DOI: 10.1016/j.bmc.2014.01.049
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2012The Selective M-1 Muscarinic Cholinergic Agonist CDD-0102A Enhances Working Memory and Cognitive Flexibility. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS. 340:588-594.Full Text via DOI: 10.1124/jpet.111.187625
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2011Multiple protein kinases determine the phosphorylated state of the small heat shock protein, HSP27, in SH-SY5Y neuroblastoma cells. NEUROPHARMACOLOGY. 61:12-24.Full Text via DOI: 10.1016/j.neuropharm.2011.02.010
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2011Theoretical studies of the solvent effect on conformational equilibria and atomic charges for isolated and hydrogen-bonded dimethoxy thiadiazoles. COMPUTATIONAL AND THEORETICAL CHEMISTRY. 966:194-206.Full Text via DOI: 10.1016/j.comptc.2011.02.034
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2011Theoretical Studies of the In-Solution Isomeric Protonation of Non-Aromatic Six-Member Rings with Two Nitrogens. JOURNAL OF PHYSICAL CHEMISTRY B. 115:4758-4767.Full Text via DOI: 10.1021/jp202241m
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2010Theoretical and Experimental Studies of the Isomeric Protonation in Solution for a Prototype Aliphatic Ring Containing Two Nitrogens. JOURNAL OF PHYSICAL CHEMISTRY B. 114:349-360.Full Text via DOI: 10.1021/jp9082085
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2007On again, off again effects of gonadectomy on the acoustic startle reflex in adult male rats. PHYSIOLOGY & BEHAVIOR. 90:473-482.Full Text via DOI: 10.1016/j.physbeh.2006.10.010
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2006Design 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-yl] Ether (CDD-0304): Effects of Structural Modifications on the Binding and Activity at Muscarinic Receptor Subtypes and Chimeras. JOURNAL OF MEDICINAL CHEMISTRY. 49:7518-7531.Full Text via DOI: 10.1021/jm0606995
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2005Classification of the mode of inhibition of high-affinity choline uptake using capillary electrophoresis with electrochemical detection at an enzyme-modified microelectrode. ANALYTICAL BIOCHEMISTRY. 339:216-222.Full Text via DOI: 10.1016/j.ab.2005.01.047
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2005Antimuscarinic Drugs for Overactive Bladder and Their Potential Effects on Cognitive Function in Older Patients. Journal of the American Geriatrics Society. 53:2195-2201.Full Text via DOI: 10.1111/j.1532-5415.2005.00537.x
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2005Theoretical Studies of the Tautomeric Equilibria for Five-Member N-Heterocycles in the Gas Phase and in Solution. JOURNAL OF PHYSICAL CHEMISTRY B. 109:22588-22602.Full Text via DOI: 10.1021/jp053076w
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2004Conformational Analysis and Derivation of Molecular Mechanics Parameters for Esters and Thioesters. JOURNAL OF PHYSICAL CHEMISTRY A. 108:10173-10185.Full Text via DOI: 10.1021/jp0490251
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2004Muscarinic acetylcholine receptors in the brain of the zebrafish (Danio rerio) measured by radioligand binding techniques. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology. 137:349-353.Full Text via DOI: 10.1016/j.cca.2004.03.002
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2003Synthesis 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. JOURNAL OF MEDICINAL CHEMISTRY. 46:4273-4286.Full Text via DOI: 10.1021/jm0301235
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2002A simple spatial alternation task for assessing memory function in zebrafish. Behavioural Processes. 58:125-132.Full Text via DOI: 10.1016/s0376-6357(02)00025-6
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2002Development of CDD-0102 as a selective M1 agonist for the treatment of Alzheimer's disease. DRUG DEVELOPMENT RESEARCH. 57:200-213.Full Text via DOI: 10.1002/ddr.10153
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2002Evaluation of the inhibition of choline uptake in synaptosomes by capillary electrophoresis with electrochemical detection. ELECTROPHORESIS. 23:3699-3704.Full Text via DOI: 10.1002/1522-2683(200211)23:21<3699::aid-elps3699>3.0.co;2-e
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2002Functional characterization of alternatively spliced 5-HT2 receptor isoforms from the pharynx and muscle of the parasitic nematode, Ascaris suum. JOURNAL OF NEUROCHEMISTRY. 83:249-258.Full Text via DOI: 10.1046/j.1471-4159.2002.01067.x
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2002Internal standard method for the measurement of choline and acetylcholine by capillary electrophoresis with electrochemical detection. JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES. 775:49-56.Full Text via DOI: 10.1016/s1570-0232(02)00269-6
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2002The utility of muscarinic agonists in the treatment of alzheimer’s disease. JOURNAL OF MOLECULAR NEUROSCIENCE. 19:187-193.Full Text via DOI: 10.1007/s12031-002-0031-5
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2001Design, Synthesis, and Biological Characterization of Bivalent 1-Methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole Derivatives as Selective Muscarinic Agonists. JOURNAL OF MEDICINAL CHEMISTRY. 44:4563-4576.Full Text via DOI: 10.1021/jm0102405
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1999Alternative-splicing of serotonin receptor isoforms in the pharynx and muscle of the parasitic nematode, Ascaris suum. MOLECULAR AND BIOCHEMICAL PARASITOLOGY. 101:95-106.Full Text via DOI: 10.1016/s0166-6851(99)00059-6
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1999First fatty acylated dipeptides to affect muscarinic receptor ligand binding. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. 9:3363-3368.Full Text via DOI: 10.1016/s0960-894x(99)00604-6
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1999Roles of threonine 192 and asparagine 382 in agonist and antagonist interactions with M1muscarinic receptors. British Journal of Pharmacology. 126:735-745.Full Text via DOI: 10.1038/sj.bjp.0702301
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1997Synthesis and Biological Characterization of 1,4,5,6-Tetrahydropyrimidine and 2-Amino-3,4,5,6-tetrahydropyridine Derivatives as Selective m1 Agonists. JOURNAL OF MEDICINAL CHEMISTRY. 40:1230-1246.Full Text via DOI: 10.1021/jm960467d
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1996Heart and T-Lymphocyte Cell Surfaces Both Exhibit Positive Cooperativity in Binding a Membrane-Lytic Toxin. JOURNAL OF MEMBRANE BIOLOGY. 150:113-122.Full Text via DOI: 10.1007/s002329900035
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1996Synthesis and biochemical activity of novel amidine derivatives as m1 muscarinic receptor agonists. BIOORGANIC & MEDICINAL CHEMISTRY. 4:1605-1615.Full Text via DOI: 10.1016/0968-0896(96)00152-6
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19951,2,5-Thiadiazole derivatives of arecoline stimulate M1 receptors coupled to phosphoinositide turnover. BRAIN RESEARCH. 693:118-123.Full Text via DOI: 10.1016/0006-8993(95)00724-5
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1995Evidence for muscarinic acetyicholine receptor subtypes in the pigeon telencephalon. JOURNAL OF COMPARATIVE NEUROLOGY. 362:271-282.Full Text via DOI: 10.1002/cne.903620209
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1994Design, Synthesis, and Neurochemical Evaluation of 2-Amino-5-(alkoxycarbonyl)-3,4,5,6-tetrahydropyridines and 2-Amino-5-(alkoxycarbonyl)-1,4,5,6-tetrahydropyrimidines as M1 Muscarinic Receptor Agonists. JOURNAL OF MEDICINAL CHEMISTRY. 37:2774-2782.Full Text via DOI: 10.1021/jm00043a016
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1993Design, synthesis, and neurochemical evaluation of 5-(3-alkyl-1,2,4-oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidines as M1 muscarinic receptor agonists. JOURNAL OF MEDICINAL CHEMISTRY. 36:842-847.Full Text via DOI: 10.1021/jm00059a008
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1993Inhibition and inactivation of presynaptic cholinergic markers using redox-reactive choline analogs. JOURNAL OF MEDICINAL CHEMISTRY. 36:1893-1901.Full Text via DOI: 10.1021/jm00065a012
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1993Regional binding of 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP) to muscarinic receptors in rat brain and comparative analysis of minimum energy conformations. NEUROCHEMISTRY INTERNATIONAL. 22:237-247.Full Text via DOI: 10.1016/0197-0186(93)90051-6
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1992Stereoselective binding and activity of oxotremorine analogs at muscarinic receptors in rat brain. Chirality. 4:463-468.Full Text via DOI: 10.1002/chir.530040802
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1992Steric and electronic requirements for muscarinic receptor-stimulated phosphoinositide turnover in the CNS in a series of arecoline bioisosteres. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. 187:1389-1394.Full Text via DOI: 10.1016/0006-291x(92)90456-u
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1992Synthesis, biochemical activity and behavioral effects of a series of 1,4,5,6-tetrahydropyrimidines as novel ligands for M1 receptors. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. 2:781-786.Full Text via DOI: 10.1016/s0960-894x(00)80531-4
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1991Involvement of the septohippocampal cholinergic system in representational memory. BRAIN RESEARCH. 564:66-72.Full Text via DOI: 10.1016/0006-8993(91)91352-2
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1991Regulation of muscarinic receptors by intrahippocampal injections of gallamine. BRAIN RESEARCH. 564:73-78.Full Text via DOI: 10.1016/0006-8993(91)91353-3
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1990Biochemical and behavioral evidence for muscarinic autoreceptors in the CNS. BRAIN RESEARCH. 517:195-201.Full Text via DOI: 10.1016/0006-8993(90)91026-d
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1990Biochemical and behavioral responses of pilocarpine at muscarinic receptor subtypes in the CNS. Comparison with receptor binding and low-energy conformations. BRAIN RESEARCH. 533:232-238.Full Text via DOI: 10.1016/0006-8993(90)91344-g
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1990Differential coupling between muscarinic receptors and G-proteins in regions of the rat brain. BIOCHEMICAL PHARMACOLOGY. 39:1385-1391.Full Text via DOI: 10.1016/0006-2952(90)90016-e
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1990Evidence for a preferential involvement of M1 muscarinic receptors in representational memory. NEUROSCIENCE LETTERS. 116:184-189.Full Text via DOI: 10.1016/0304-3940(90)90407-z
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1990Identification of four brain areas each enriched in a unique muscarinic receptor subtype. LIFE SCIENCES. 46:1051-1058.Full Text via DOI: 10.1016/0024-3205(90)90413-l
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1990Subtype specificity of the muscarinic receptor-stimulated GTPase response in the rat cortex. NEUROSCIENCE LETTERS. 110:148-154.Full Text via DOI: 10.1016/0304-3940(90)90803-h
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1989Autoradiographic analyses of agonist binding to muscarinic receptor subtypes. BIOCHEMICAL PHARMACOLOGY. 38:837-850.Full Text via DOI: 10.1016/0006-2952(89)90239-6
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1989Interaction of amitriptyline with muscarinic receptor subtypes in the rat brain. NEUROCHEMISTRY INTERNATIONAL. 14:447-454.Full Text via DOI: 10.1016/0197-0186(89)90034-x
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1989Regional differences in the binding of selective muscarinic receptor antagonists in rat brain: comparison with minimum-energy conformations. JOURNAL OF MEDICINAL CHEMISTRY. 32:1164-1172.Full Text via DOI: 10.1021/jm00126a004
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1988Intrahippocampal injections of gallamine impair learning of a memory task. NEUROSCIENCE LETTERS. 89:367-372.Full Text via DOI: 10.1016/0304-3940(88)90554-x
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1987Selectivity of pirenzepine in the central nervous system. I. Direct autoradiographic comparison of the regional distribution of pirenzepine and carbamylcholine binding sites. BRAIN RESEARCH. 407:27-36.Full Text via DOI: 10.1016/0006-8993(87)91216-9
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1987Selectivity of pirenzepine in the central nervous system. II. Differential effects of pirenzepine and scopolamine on performance of a representational memory task. BRAIN RESEARCH. 407:37-45.Full Text via DOI: 10.1016/0006-8993(87)91217-0
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1986Regional distribution of muscarinic receptors preferring gallamine in the rat brain. BIOCHEMICAL PHARMACOLOGY. 35:4171-4176.Full Text via DOI: 10.1016/0006-2952(86)90692-1
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Editorial Material (Web of Science)
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1986Multiple muscarinic receptors in the CNS. BIOCHEMICAL PHARMACOLOGY. 3895-3901.Full Text via DOI: 10.1016/0006-2952(86)90001-8
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Meeting Abstract (Web of Science)
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2011Structure activity relationships in a series of potential allosteric muscarinic ligands. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY.
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1999Activity of selective muscarinic agonists at human M1 receptors expressed at varying levels in A9 L cells. LIFE SCIENCES. 571.Full Text via DOI: 10.1016/s0024-3205(99)90498-8
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1999Mutant M1 muscarinic receptors with enhanced agonist activity. LIFE SCIENCES. 563.Full Text via DOI: 10.1016/s0024-3205(99)90481-2
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1999Mutant M1 muscarinic receptors with increased agonist affinity and G protein coupling. LIFE SCIENCES. 563.Full Text via DOI: 10.1016/s0024-3205(99)90482-4
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1995Neurochemical evaluation of the selective m1 muscarinic receptor agonist CDD-0097-A. LIFE SCIENCES. 1005.Full Text via DOI: 10.1016/0024-3205(95)93723-r
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1995Selectivity of 2-amino-5-alkoxycarbonyl-3,4,5,6-tetrahydropyridines and 2-amino-5-alkoxycarbonyl-1,4,5,6-tetrahydropyrimidines for muscarinic receptor subtypes. LIFE SCIENCES. 1007.Full Text via DOI: 10.1016/0024-3205(95)93726-u
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1995Synthesis and structure-activity relationships of novel amidine derivatives as muscarinic receptor subtype-selective agonists. LIFE SCIENCES. 1005.Full Text via DOI: 10.1016/0024-3205(95)93722-q
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Review Article (Web of Science)
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2008Electrochemical detection of acetylcholine and choline: application to the quantitative nonradiochemical evaluation of choline transport. ANALYTICAL AND BIOANALYTICAL CHEMISTRY. 651-662.Full Text via DOI: 10.1007/s00216-008-2307-2
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Contact
full name
- William S Messer