Thomas Bridges, Ph.D.

Research Assistant Professor

thomas.m.bridges@vanderbilt.edu
Faculty Appointments
Research Assistant Professor of Pharmacology
Education
Ph.D., Pharmacology, Vanderbilt University, Nashville, TennesseeB.S., Biology, Wheaton College , Wheaton, Illinois
Publications
Wood MR, Noetzel MJ, Tarr JC, Rodriguez AL, Lamsal A, Chang S, Foster JJ, Smith E, Chase P, Hodder PS, Engers DW, Niswender CM, Brandon NJ, Wood MW, Duggan ME, Conn PJ, Bridges TM, Lindsley CW. Discovery and SAR of a novel series of potent, CNS penetrant M4 PAMs based on a non-enolizable ketone core: Challenges in disposition. Bioorg. Med. Chem. Lett [print-electronic]. 2016 Sep 9/1/2016; 26(17): 4282-6. PMID: 27476142, PMCID: PMC4987221, PII: S0960-894X(16)30755-7, DOI: 10.1016/j.bmcl.2016.07.042, ISSN: 1464-3405.

Wood MR, Noetzel MJ, Engers JL, Bollinger KA, Melancon BJ, Tarr JC, Han C, West M, Gregro AR, Lamsal A, Chang S, Ajmera S, Smith E, Chase P, Hodder PS, Bubser M, Jones CK, Hopkins CR, Emmitte KA, Niswender CM, Wood MW, Duggan ME, Conn PJ, Bridges TM, Lindsley CW. Discovery and optimization of a novel series of highly CNS penetrant M4 PAMs based on a 5,6-dimethyl-4-(piperidin-1-yl)thieno[2,3-d]pyrimidine core. Bioorg. Med. Chem. Lett [print-electronic]. 2016 Jul 7/1/2016; 26(13): 3029-33. PMID: 27185330, PMCID: PMC4955361, PII: S0960-894X(16)30490-5, DOI: 10.1016/j.bmcl.2016.05.010, ISSN: 1464-3405.

Gogliotti RG, Klar R, Rook JM, Ghoshal A, Zamorano R, Malosh C, Stauffer SR, Bridges TM, Bartolome JM, Daniels JS, Jones C, Lindsley CW, Conn PJ, Niswender CM. MGlu5 Positive Allosteric Modulation Normalizes Synaptic Plasticity Defects and Motor Phenotypes in a Mouse Model of Rett Syndrome. Hum. Mol. Genet [print-electronic]. 2016 Mar 3/2/2016; PMID: 26936821, PII: ddw074, DOI: 10.1093/hmg/ddw074, ISSN: 1460-2083.

Gould RW, Nedelcovych MT, Gong X, Tsai E, Bubser M, Bridges TM, Wood MR, Duggan ME, Brandon NJ, Dunlop J, Wood MW, Ivarsson M, Noetzel MJ, Daniels JS, Niswender CM, Lindsley CW, Conn PJ, Jones CK. State-dependent alterations in sleep/wake architecture elicited by the M4 PAM VU0467154 - Relation to antipsychotic-like drug effects. Neuropharmacology [print-electronic]. 2016 Mar; 102: 244-53. PMID: 26617071, PII: S0028-3908(15)30180-5, DOI: 10.1016/j.neuropharm.2015.11.016, ISSN: 1873-7064.

Conde-Ceide S, Alcázar J, Alonso de Diego SA, López S, Martín-Martín ML, Martínez-Viturro CM, Pena MA, Tong HM, Lavreysen H, Mackie C, Bridges TM, Daniels JS, Niswender CM, Jones CK, Macdonald GJ, Steckler T, Conn PJ, Stauffer SR, Lindsley CW, Bartolomé-Nebreda JM. Preliminary investigation of 6,7-dihydropyrazolo[1,5-a]pyrazin-4-one derivatives as a novel series of mGlu5 receptor positive allosteric modulators with efficacy in preclinical models of schizophrenia. Bioorg. Med. Chem. Lett [print-electronic]. 2016 Jan 1/15/2016; 26(2): 429-34. PMID: 26684851, PII: S0960-894X(15)30306-1, DOI: 10.1016/j.bmcl.2015.11.098, ISSN: 1464-3405.

Malosh C, Turlington M, Bridges TM, Rook JM, Noetzel MJ, Vinson PN, Steckler T, Lavreysen H, Mackie C, Bartolomé-Nebreda JM, Conde-Ceide S, Martínez-Viturro CM, Piedrafita M, Sánchez-Casado MR, Macdonald GJ, Daniels JS, Jones CK, Niswender CM, Conn PJ, Lindsley CW, Stauffer SR. Acyl dihydropyrazolo[1,5-a]pyrimidinones as metabotropic glutamate receptor 5 positive allosteric modulators. Bioorg. Med. Chem. Lett [print-electronic]. 2015 Nov 11/15/2015; 25(22): 5115-20. PMID: 26475522, PMCID: PMC4634704, PII: S0960-894X(15)30118-9, DOI: 10.1016/j.bmcl.2015.10.009, ISSN: 1464-3405.

Pancani T, Foster DJ, Moehle MS, Bichell TJ, Bradley E, Bridges TM, Klar R, Poslusney M, Rook JM, Daniels JS, Niswender CM, Jones CK, Wood MR, Bowman AB, Lindsley CW, Xiang Z, Conn PJ. Allosteric activation of M4 muscarinic receptors improve behavioral and physiological alterations in early symptomatic YAC128 mice. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2015 Nov 11/10/2015; 112(45): 14078-83. PMID: 26508634, PMCID: PMC4653197, PII: 1512812112, DOI: 10.1073/pnas.1512812112, ISSN: 1091-6490.

Blobaum AL, Byers FW, Bridges TM, Locuson CW, Conn PJ, Lindsley CW, Daniels JS. A Screen of Approved Drugs Identifies the Androgen Receptor Antagonist Flutamide and Its Pharmacologically Active Metabolite 2-Hydroxy-Flutamide as Heterotropic Activators of Cytochrome P450 3A In Vitro and In Vivo. Drug Metab. Dispos [print-electronic]. 2015 Nov; 43(11): 1718-26. PMID: 26265743, PMCID: PMC4613951, PII: dmd.115.064006, DOI: 10.1124/dmd.115.064006, ISSN: 1521-009X.

Zhou Y, Malosh C, Conde-Ceide S, Martínez-Viturro CM, Alcázar J, Lavreysen H, Mackie C, Bridges TM, Daniels JS, Niswender CM, Jones CK, Macdonald GJ, Steckler T, Conn PJ, Stauffer SR, Bartolomé-Nebreda JM, Lindsley CW. Further optimization of the mGlu5 PAM clinical candidate VU0409551/JNJ-46778212: Progress and challenges towards a back-up compound. Bioorg. Med. Chem. Lett [print-electronic]. 2015 Sep 9/1/2015; 25(17): 3515-9. PMID: 26183084, PMCID: PMC4535329, PII: S0960-894X(15)00701-5, DOI: 10.1016/j.bmcl.2015.06.096, ISSN: 1464-3405.

Conde-Ceide S, Martínez-Viturro CM, Alcázar J, Garcia-Barrantes PM, Lavreysen H, Mackie C, Vinson PN, Rook JM, Bridges TM, Daniels JS, Megens A, Langlois X, Drinkenburg WH, Ahnaou A, Niswender CM, Jones CK, Macdonald GJ, Steckler T, Conn PJ, Stauffer SR, Bartolomé-Nebreda JM, Lindsley CW. Discovery of VU0409551/JNJ-46778212: An mGlu5 Positive Allosteric Modulator Clinical Candidate Targeting Schizophrenia. ACS Med Chem Lett. 2015 Jun 6/11/2015; 6(6): 716-20. PMID: 26157544, PMCID: PMC4492464, DOI: 10.1021/acsmedchemlett.5b00181, ISSN: 1948-5875.

Rook JM, Xiang Z, Lv X, Ghoshal A, Dickerson JW, Bridges TM, Johnson KA, Foster DJ, Gregory KJ, Vinson PN, Thompson AD, Byun N, Collier RL, Bubser M, Nedelcovych MT, Gould RW, Stauffer SR, Daniels JS, Niswender CM, Lavreysen H, Mackie C, Conde-Ceide S, Alcazar J, Bartolomé-Nebreda JM, Macdonald GJ, Talpos JC, Steckler T, Jones CK, Lindsley CW, Conn PJ. Biased mGlu5-Positive Allosteric Modulators Provide In Vivo Efficacy without Potentiating mGlu5 Modulation of NMDAR Currents. Neuron [print-electronic]. 2015 May 5/20/2015; 86(4): 1029-40. PMID: 25937172, PMCID: PMC4443790, PII: S0896-6273(15)00287-1, DOI: 10.1016/j.neuron.2015.03.063, ISSN: 1097-4199.

Martín-Martín ML, Bartolomé-Nebreda JM, Conde-Ceide S, Alonso de Diego SA, López S, Martínez-Viturro CM, Tong HM, Lavreysen H, Macdonald GJ, Steckler T, Mackie C, Bridges TM, Daniels JS, Niswender CM, Noetzel MJ, Jones CK, Conn PJ, Lindsley CW, Stauffer SR. Discovery and SAR of novel series of imidazopyrimidinones and dihydroimidazopyrimidinones as positive allosteric modulators of the metabotropic glutamate receptor 5 (mGlu5). Bioorg. Med. Chem. Lett [print-electronic]. 2015 Mar 3/15/2015; 25(6): 1310-7. PMID: 25683622, PMCID: PMC4399811, PII: S0960-894X(15)00050-5, DOI: 10.1016/j.bmcl.2015.01.038, ISSN: 1464-3405.

Kurata H, Gentry PR, Kokubo M, Cho HP, Bridges TM, Niswender CM, Byers FW, Wood MR, Daniels JS, Conn PJ, Lindsley CW. Further optimization of the M5 NAM MLPCN probe ML375: tactics and challenges. Bioorg. Med. Chem. Lett [print-electronic]. 2015 Feb 2/1/2015; 25(3): 690-4. PMID: 25542588, PMCID: PMC4535335, PII: S0960-894X(14)01289-X, DOI: 10.1016/j.bmcl.2014.11.082, ISSN: 1464-3405.

Bridges TM, Morrison RD, Byers FW, Luo S, Scott Daniels J. Use of a novel rapid and resource-efficient cassette dosing approach to determine the pharmacokinetics and CNS distribution of small molecule 7-transmembrane receptor allosteric modulators in rat. Pharmacol Res Perspect [print-electronic]. 2014 Dec; 2(6): e00077. PMID: 25505618, PMCID: PMC4186453, DOI: 10.1002/prp2.77, ISSN: 2052-1707.

Bubser M, Bridges TM, Dencker D, Gould RW, Grannan M, Noetzel MJ, Lamsal A, Niswender CM, Daniels JS, Poslusney MS, Melancon BJ, Tarr JC, Byers FW, Wess J, Duggan ME, Dunlop J, Wood MW, Brandon NJ, Wood MR, Lindsley CW, Conn PJ, Jones CK. Selective activation of M4 muscarinic acetylcholine receptors reverses MK-801-induced behavioral impairments and enhances associative learning in rodents. ACS Chem Neurosci [print-electronic]. 2014 Oct 10/15/2014; 5(10): 920-42. PMID: 25137629, PMCID: PMC4324418, DOI: 10.1021/cn500128b, ISSN: 1948-7193.

Gentry PR, Kokubo M, Bridges TM, Noetzel MJ, Cho HP, Lamsal A, Smith E, Chase P, Hodder PS, Niswender CM, Daniels JS, Conn PJ, Lindsley CW, Wood MR. Development of a highly potent, novel M5 positive allosteric modulator (PAM) demonstrating CNS exposure: 1-((1H-indazol-5-yl)sulfoneyl)-N-ethyl-N-(2-(trifluoromethyl)benzyl)piperidine-4-carboxamide (ML380). J. Med. Chem [print-electronic]. 2014 Sep 9/25/2014; 57(18): 7804-10. PMID: 25147929, PMCID: PMC4175000, DOI: 10.1021/jm500995y, ISSN: 1520-4804.

Turlington M, Noetzel MJ, Bridges TM, Vinson PN, Steckler T, Lavreysen H, Mackie C, Bartolomé-Nebreda JM, Conde-Ceide S, Tong HM, Macdonald GJ, Daniels JS, Jones CK, Niswender CM, Conn PJ, Lindsley CW, Stauffer SR. Discovery and SAR of a novel series of metabotropic glutamate receptor 5 positive allosteric modulators with high ligand efficiency. Bioorg. Med. Chem. Lett [print-electronic]. 2014 Aug 8/1/2014; 24(15): 3641-6. PMID: 24961642, PMCID: PMC4234308, PII: S0960-894X(14)00444-2, DOI: 10.1016/j.bmcl.2014.04.087, ISSN: 1464-3405.

Gentry PR, Kokubo M, Bridges TM, Cho HP, Smith E, Chase P, Hodder PS, Utley TJ, Rajapakse A, Byers F, Niswender CM, Morrison RD, Daniels JS, Wood MR, Conn PJ, Lindsley CW. Discovery, synthesis and characterization of a highly muscarinic acetylcholine receptor (mAChR)-selective M5-orthosteric antagonist, VU0488130 (ML381): a novel molecular probe. ChemMedChem [print-electronic]. 2014 Aug; 9(8): 1677-82. PMID: 24692176, PMCID: PMC4116439, DOI: 10.1002/cmdc.201402051, ISSN: 1860-7187.

Byun NE, Grannan M, Bubser M, Barry RL, Thompson A, Rosanelli J, Gowrishankar R, Kelm ND, Damon S, Bridges TM, Melancon BJ, Tarr JC, Brogan JT, Avison MJ, Deutch AY, Wess J, Wood MR, Lindsley CW, Gore JC, Conn PJ, Jones CK. Antipsychotic drug-like effects of the selective M4 muscarinic acetylcholine receptor positive allosteric modulator VU0152100. Neuropsychopharmacology [print-electronic]. 2014 Jun; 39(7): 1578-93. PMID: 24442096, PMCID: PMC4023154, PII: npp20142, DOI: 10.1038/npp.2014.2, ISSN: 1740-634X.

Foster DJ, Gentry PR, Lizardi-Ortiz JE, Bridges TM, Wood MR, Niswender CM, Sulzer D, Lindsley CW, Xiang Z, Conn PJ. M5 receptor activation produces opposing physiological outcomes in dopamine neurons depending on the receptor's location. J. Neurosci. 2014 Feb 2/26/2014; 34(9): 3253-62. PMID: 24573284, PMCID: PMC3935086, PII: 34/9/3253, DOI: 10.1523/JNEUROSCI.4896-13.2014, ISSN: 1529-2401.

Blobaum AL, Bridges TM, Byers FW, Turlington ML, Mattmann ME, Morrison RD, Mackie C, Lavreysen H, Bartolomé JM, Macdonald GJ, Steckler T, Jones CK, Niswender CM, Conn PJ, Lindsley CW, Stauffer SR, Daniels JS. Heterotropic activation of the midazolam hydroxylase activity of CYP3A by a positive allosteric modulator of mGlu5: in vitro to in vivo translation and potential impact on clinically relevant drug-drug interactions. Drug Metab. Dispos [print-electronic]. 2013 Dec; 41(12): 2066-75. PMID: 24003250, PMCID: PMC3834130, PII: dmd.113.052662, DOI: 10.1124/dmd.113.052662, ISSN: 1521-009X.

Gentry PR, Kokubo M, Bridges TM, Kett NR, Harp JM, Cho HP, Smith E, Chase P, Hodder PS, Niswender CM, Daniels JS, Conn PJ, Wood MR, Lindsley CW. Discovery of the first M5-selective and CNS penetrant negative allosteric modulator (NAM) of a muscarinic acetylcholine receptor: (S)-9b-(4-chlorophenyl)-1-(3,4-difluorobenzoyl)-2,3-dihydro-1H-imidazo[2,1-a]isoindol-5(9bH)-one (ML375). J. Med. Chem [print-electronic]. 2013 Nov 11/27/2013; 56(22): 9351-5. PMID: 24164599, PMCID: PMC3876027, DOI: 10.1021/jm4013246, ISSN: 1520-4804.

Gregory KJ, Herman EJ, Ramsey AJ, Hammond AS, Byun NE, Stauffer SR, Manka JT, Jadhav S, Bridges TM, Weaver CD, Niswender CM, Steckler T, Drinkenburg WH, Ahnaou A, Lavreysen H, Macdonald GJ, Bartolomé JM, Mackie C, Hrupka BJ, Caron MG, Daigle TL, Lindsley CW, Conn PJ, Jones CK. N-aryl piperazine metabotropic glutamate receptor 5 positive allosteric modulators possess efficacy in preclinical models of NMDA hypofunction and cognitive enhancement. J. Pharmacol. Exp. Ther [print-electronic]. 2013 Nov; 347(2): 438-57. PMID: 23965381, PMCID: PMC3807069, PII: jpet.113.206623, DOI: 10.1124/jpet.113.206623, ISSN: 1521-0103.

Turlington M, Noetzel MJ, Chun A, Zhou Y, Gogliotti RD, Nguyen ED, Gregory KJ, Vinson PN, Rook JM, Gogi KK, Xiang Z, Bridges TM, Daniels JS, Jones C, Niswender CM, Meiler J, Conn PJ, Lindsley CW, Stauffer SR. Exploration of allosteric agonism structure-activity relationships within an acetylene series of metabotropic glutamate receptor 5 (mGlu5) positive allosteric modulators (PAMs): discovery of 5-((3-fluorophenyl)ethynyl)-N-(3-methyloxetan-3-yl)picolinamide (ML254). J. Med. Chem [print-electronic]. 2013 Oct 10/24/2013; 56(20): 7976-96. PMID: 24050755, PMCID: PMC3908770, DOI: 10.1021/jm401028t, ISSN: 1520-4804.

Bridges TM, Rook JM, Noetzel MJ, Morrison RD, Zhou Y, Gogliotti RD, Vinson PN, Xiang Z, Jones CK, Niswender CM, Lindsley CW, Stauffer SR, Conn PJ, Daniels JS. Biotransformation of a novel positive allosteric modulator of metabotropic glutamate receptor subtype 5 contributes to seizure-like adverse events in rats involving a receptor agonism-dependent mechanism. Drug Metab. Dispos [print-electronic]. 2013 Sep; 41(9): 1703-14. PMID: 23821185, PMCID: PMC3876804, PII: dmd.113.052084, DOI: 10.1124/dmd.113.052084, ISSN: 1521-009X.

Gentry PR, Bridges TM, Lamsal A, Vinson PN, Smith E, Chase P, Hodder PS, Engers JL, Niswender CM, Daniels JS, Conn PJ, Wood MR, Lindsley CW. Discovery of ML326: The first sub-micromolar, selective M5 PAM. Bioorg. Med. Chem. Lett [print-electronic]. 2013 May 5/15/2013; 23(10): 2996-3000. PMID: 23562060, PMCID: PMC3634896, PII: S0960-894X(13)00348-X, DOI: 10.1016/j.bmcl.2013.03.032, ISSN: 1464-3405.

Poslusney MS, Melancon BJ, Gentry PR, Sheffler DJ, Bridges TM, Utley TJ, Daniels JS, Niswender CM, Conn PJ, Lindsley CW, Wood MR. Spirocyclic replacements for the isatin in the highly selective, muscarinic M1 PAM ML137: the continued optimization of an MLPCN probe molecule. Bioorg. Med. Chem. Lett [print-electronic]. 2013 Mar 3/15/2013; 23(6): 1860-4. PMID: 23416001, PMCID: PMC3594472, PII: S0960-894X(13)00039-5, DOI: 10.1016/j.bmcl.2013.01.017, ISSN: 1464-3405.

Rook JM, Noetzel MJ, Pouliot WA, Bridges TM, Vinson PN, Cho HP, Zhou Y, Gogliotti RD, Manka JT, Gregory KJ, Stauffer SR, Dudek FE, Xiang Z, Niswender CM, Daniels JS, Jones CK, Lindsley CW, Conn PJ. Unique signaling profiles of positive allosteric modulators of metabotropic glutamate receptor subtype 5 determine differences in in vivo activity. Biol. Psychiatry [print-electronic]. 2013 Mar 3/15/2013; 73(6): 501-9. PMID: 23140665, PMCID: PMC3572342, PII: S0006-3223(12)00806-2, DOI: 10.1016/j.biopsych.2012.09.012, ISSN: 1873-2402.

Melancon BJ, Poslusney MS, Gentry PR, Tarr JC, Sheffler DJ, Mattmann ME, Bridges TM, Utley TJ, Daniels JS, Niswender CM, Conn PJ, Lindsley CW, Wood MR. Isatin replacements applied to the highly selective, muscarinic M1 PAM ML137: continued optimization of an MLPCN probe molecule. Bioorg. Med. Chem. Lett [print-electronic]. 2013 Jan 1/15/2013; 23(2): 412-6. PMID: 23237839, PMCID: PMC3534865, PII: S0960-894X(12)01544-2, DOI: 10.1016/j.bmcl.2012.11.092, ISSN: 1464-3405.

Downey JD, Saleh SA, Bridges TM, Morrison RD, Daniels JS, Lindsley CW, Breyer RM. Development of an in vivo active, dual EP1 and EP3 selective antagonist based on a novel acyl sulfonamide bioisostere. Bioorg. Med. Chem. Lett [print-electronic]. 2013 Jan 1/1/2013; 23(1): 37-41. PMID: 23218714, PMCID: PMC3534858, PII: S0960-894X(12)01498-9, DOI: 10.1016/j.bmcl.2012.11.046, ISSN: 1464-3405.

Le U, Melancon BJ, Bridges TM, Vinson PN, Utley TJ, Lamsal A, Rodriguez AL, Venable D, Sheffler DJ, Jones CK, Blobaum AL, Wood MR, Daniels JS, Conn PJ, Niswender CM, Lindsley CW, Hopkins CR. Discovery of a selective M4 positive allosteric modulator based on the 3-amino-thieno[2,3-b]pyridine-2-carboxamide scaffold: development of ML253, a potent and brain penetrant compound that is active in a preclinical model of schizophrenia. Bioorg. Med. Chem. Lett [print-electronic]. 2013 Jan 1/1/2013; 23(1): 346-50. PMID: 23177787, PMCID: PMC3535830, PII: S0960-894X(12)01364-9, DOI: 10.1016/j.bmcl.2012.10.073, ISSN: 1464-3405.

Digby GJ, Utley TJ, Lamsal A, Sevel C, Sheffler DJ, Lebois EP, Bridges TM, Wood MR, Niswender CM, Lindsley CW, Conn PJ. Chemical modification of the M(1) agonist VU0364572 reveals molecular switches in pharmacology and a bitopic binding mode. ACS Chem Neurosci [print-electronic]. 2012 Dec 12/19/2012; 3(12): 1025-36. PMID: 23259038, PMCID: PMC3526969, DOI: 10.1021/cn300103e, ISSN: 1948-7193.

Tarr JC, Turlington ML, Reid PR, Utley TJ, Sheffler DJ, Cho HP, Klar R, Pancani T, Klein MT, Bridges TM, Morrison RD, Blobaum AL, Xiang Z, Daniels JS, Niswender CM, Conn PJ, Wood MR, Lindsley CW. Targeting selective activation of M(1) for the treatment of Alzheimer's disease: further chemical optimization and pharmacological characterization of the M(1) positive allosteric modulator ML169. ACS Chem Neurosci [print-electronic]. 2012 Nov 11/21/2012; 3(11): 884-95. PMID: 23173069, PMCID: PMC3503349, DOI: 10.1021/cn300068s, ISSN: 1948-7193.

Poslusney MS, Sevel C, Utley TJ, Bridges TM, Morrison RD, Kett NR, Sheffler DJ, Niswender CM, Daniels JS, Conn PJ, Lindsley CW, Wood MR. Synthesis and biological characterization of a series of novel diaryl amide M1 antagonists. Bioorg. Med. Chem. Lett [print-electronic]. 2012 Nov 11/15/2012; 22(22): 6923-8. PMID: 23062550, PMCID: PMC3897205, PII: S0960-894X(12)01155-9, DOI: 10.1016/j.bmcl.2012.09.011, ISSN: 1464-3405.

Morrison RD, Blobaum AL, Byers FW, Santomango TS, Bridges TM, Stec D, Brewer KA, Sanchez-Ponce R, Corlew MM, Rush R, Felts AS, Manka J, Bates BS, Venable DF, Rodriguez AL, Jones CK, Niswender CM, Conn PJ, Lindsley CW, Emmitte KA, Daniels JS. The role of aldehyde oxidase and xanthine oxidase in the biotransformation of a novel negative allosteric modulator of metabotropic glutamate receptor subtype 5. Drug Metab. Dispos [print-electronic]. 2012 Sep; 40(9): 1834-45. PMID: 22711749, PMCID: PMC3422546, PII: dmd.112.046136, DOI: 10.1124/dmd.112.046136, ISSN: 1521-009X.

Melancon BJ, Utley TJ, Sevel C, Mattmann ME, Cheung YY, Bridges TM, Morrison RD, Sheffler DJ, Niswender CM, Daniels JS, Conn PJ, Lindsley CW, Wood MR. Development of novel M1 antagonist scaffolds through the continued optimization of the MLPCN probe ML012. Bioorg. Med. Chem. Lett [print-electronic]. 2012 Aug 8/1/2012; 22(15): 5035-40. PMID: 22749871, PMCID: PMC3883446, PII: S0960-894X(12)00765-2, DOI: 10.1016/j.bmcl.2012.06.018, ISSN: 1464-3405.

Salovich JM, Vinson PN, Sheffler DJ, Lamsal A, Utley TJ, Blobaum AL, Bridges TM, Le U, Jones CK, Wood MR, Daniels JS, Conn PJ, Niswender CM, Lindsley CW, Hopkins CR. Discovery of N-(4-methoxy-7-methylbenzo[d]thiazol-2-yl)isonicatinamide, ML293, as a novel, selective and brain penetrant positive allosteric modulator of the muscarinic 4 (M4) receptor. Bioorg. Med. Chem. Lett [print-electronic]. 2012 Aug 8/1/2012; 22(15): 5084-8. PMID: 22738637, PMCID: PMC3401285, PII: S0960-894X(12)00721-4, DOI: 10.1016/j.bmcl.2012.05.109, ISSN: 1464-3405.

Melancon BJ, Gogliotti RD, Tarr JC, Saleh SA, Chauder BA, Lebois EP, Cho HP, Utley TJ, Sheffler DJ, Bridges TM, Morrison RD, Daniels JS, Niswender CM, Conn PJ, Lindsley CW, Wood MR. Continued optimization of the MLPCN probe ML071 into highly potent agonists of the hM1 muscarinic acetylcholine receptor. Bioorg. Med. Chem. Lett [print-electronic]. 2012 May 5/15/2012; 22(10): 3467-72. PMID: 22507963, PMCID: PMC3348459, PII: S0960-894X(12)00409-X, DOI: 10.1016/j.bmcl.2012.03.088, ISSN: 1464-3405.

Jones CK, Bubser M, Thompson AD, Dickerson JW, Turle-Lorenzo N, Amalric M, Blobaum AL, Bridges TM, Morrison RD, Jadhav S, Engers DW, Italiano K, Bode J, Daniels JS, Lindsley CW, Hopkins CR, Conn PJ, Niswender CM. The metabotropic glutamate receptor 4-positive allosteric modulator VU0364770 produces efficacy alone and in combination with L-DOPA or an adenosine 2A antagonist in preclinical rodent models of Parkinson's disease. J. Pharmacol. Exp. Ther [print-electronic]. 2012 Feb; 340(2): 404-21. PMID: 22088953, PMCID: PMC3263969, PII: jpet.111.187443, DOI: 10.1124/jpet.111.187443, ISSN: 1521-0103.

Melancon BJ, Lamers AP, Bridges TM, Sulikowski GA, Utley TJ, Sheffler DJ, Noetzel MJ, Morrison RD, Daniels JS, Niswender CM, Jones CK, Conn PJ, Lindsley CW, Wood MR. Development of a more highly selective M(1) antagonist from the continued optimization of the MLPCN Probe ML012. Bioorg. Med. Chem. Lett [print-electronic]. 2012 Jan 1/15/2012; 22(2): 1044-8. PMID: 22197142, PMCID: PMC3434972, PII: S0960-894X(11)01654-4, DOI: 10.1016/j.bmcl.2011.11.110, ISSN: 1464-3405.

Lebois EP, Digby GJ, Sheffler DJ, Melancon BJ, Tarr JC, Cho HP, Miller NR, Morrison R, Bridges TM, Xiang Z, Daniels JS, Wood MR, Conn PJ, Lindsley CW. Development of a highly selective, orally bioavailable and CNS penetrant M1 agonist derived from the MLPCN probe ML071. Bioorg. Med. Chem. Lett [print-electronic]. 2011 Nov 11/1/2011; 21(21): 6451-5. PMID: 21930376, PMCID: PMC3190051, PII: S0960-894X(11)01183-8, DOI: 10.1016/j.bmcl.2011.08.084, ISSN: 1464-3405.

Reid PR, Bridges TM, Sheffler DJ, Cho HP, Lewis LM, Days E, Daniels JS, Jones CK, Niswender CM, Weaver CD, Conn PJ, Lindsley CW, Wood MR. Discovery and optimization of a novel, selective and brain penetrant M1 positive allosteric modulator (PAM): the development of ML169, an MLPCN probe. Bioorg. Med. Chem. Lett [print-electronic]. 2011 May 5/1/2011; 21(9): 2697-701. PMID: 21194936, PMCID: PMC3082000, PII: S0960-894X(10)01769-5, DOI: 10.1016/j.bmcl.2010.12.015, ISSN: 1464-3405.

Bridges TM, Kennedy JP, Hopkins CR, Conn PJ, Lindsley CW. Heterobiaryl and heterobiaryl ether derived M5 positive allosteric modulators. Bioorg. Med. Chem. Lett [print-electronic]. 2010 Oct 10/1/2010; 20(19): 5617-22. PMID: 20801651, PMCID: PMC3179183, PII: S0960-894X(10)01165-0, DOI: 10.1016/j.bmcl.2010.08.042, ISSN: 1464-3405.

Bridges TM, LeBois EP, Hopkins CR, Wood MR, Jones CK, Conn PJ, Lindsley CW. The antipsychotic potential of muscarinic allosteric modulation. Drug News Perspect. 2010 May; 23(4): 229-40. PMID: 20520852, PMCID: PMC4780339, PII: 1416977, DOI: 10.1358/dnp.2010.23.4.1416977, ISSN: 0214-0934.

Bridges TM, Phillip Kennedy J, Noetzel MJ, Breininger ML, Gentry PR, Conn PJ, Lindsley CW. Chemical lead optimization of a pan Gq mAChR M1, M3, M5 positive allosteric modulator (PAM) lead. Part II: development of a potent and highly selective M1 PAM. Bioorg. Med. Chem. Lett [print-electronic]. 2010 Mar 3/15/2010; 20(6): 1972-5. PMID: 20156687, PMCID: PMC2834874, PII: S0960-894X(10)00121-6, DOI: 10.1016/j.bmcl.2010.01.109, ISSN: 1464-3405.

Bridges TM, Kennedy JP, Cho HP, Breininger ML, Gentry PR, Hopkins CR, Conn PJ, Lindsley CW. Chemical lead optimization of a pan G(q) mAChR M(1), M(3), M(5) positive allosteric modulator (PAM) lead. Part I: Development of the first highly selective M(5) PAM. Bioorg. Med. Chem. Lett [print-electronic]. 2010 Jan 1/15/2010; 20(2): 558-62. PMID: 20004578, PMCID: PMC3177601, PII: S0960-894X(09)01659-X, DOI: 10.1016/j.bmcl.2009.11.089, ISSN: 1464-3405.

Lebois EP, Bridges TM, Lewis LM, Dawson ES, Kane AS, Xiang Z, Jadhav SB, Yin H, Kennedy JP, Meiler J, Niswender CM, Jones CK, Conn PJ, Weaver CD, Lindsley CW. Discovery and characterization of novel subtype-selective allosteric agonists for the investigation of M(1) receptor function in the central nervous system. ACS Chem Neurosci. 2010; 1(2): 104-21. PMID: 21961051, PMCID: PMC3180826, DOI: 10.1021/cn900003h, ISSN: 1948-7193.

Shirey JK, Brady AE, Jones PJ, Davis AA, Bridges TM, Kennedy JP, Jadhav SB, Menon UN, Xiang Z, Watson ML, Christian EP, Doherty JJ, Quirk MC, Snyder DH, Lah JJ, Levey AI, Nicolle MM, Lindsley CW, Conn PJ. A selective allosteric potentiator of the M1 muscarinic acetylcholine receptor increases activity of medial prefrontal cortical neurons and restores impairments in reversal learning. J. Neurosci. 2009 Nov 11/11/2009; 29(45): 14271-86. PMID: 19906975, PMCID: PMC2811323, PII: 29/45/14271, DOI: 10.1523/JNEUROSCI.3930-09.2009, ISSN: 1529-2401.

Kennedy JP, Bridges TM, Gentry PR, Brogan JT, Kane AS, Jones CK, Brady AE, Shirey JK, Conn PJ, Lindsley CW. Synthesis and structure-activity relationships of allosteric potentiators of the m(4) muscarinic acetylcholine receptor. ChemMedChem. 2009 Oct; 4(10): 1600-7. PMID: 19705385, PMCID: PMC2887613, DOI: 10.1002/cmdc.200900231, ISSN: 1860-7187.

Sheffler DJ, Williams R, Bridges TM, Xiang Z, Kane AS, Byun NE, Jadhav S, Mock MM, Zheng F, Lewis LM, Jones CK, Niswender CM, Weaver CD, Lindsley CW, Conn PJ. A novel selective muscarinic acetylcholine receptor subtype 1 antagonist reduces seizures without impairing hippocampus-dependent learning. Mol. Pharmacol [print-electronic]. 2009 Aug; 76(2): 356-68. PMID: 19407080, PMCID: PMC2713127, PII: mol.109.056531, DOI: 10.1124/mol.109.056531, ISSN: 1521-0111.

Bridges TM, Marlo JE, Niswender CM, Jones CK, Jadhav SB, Gentry PR, Plumley HC, Weaver CD, Conn PJ, Lindsley CW. Discovery of the first highly M5-preferring muscarinic acetylcholine receptor ligand, an M5 positive allosteric modulator derived from a series of 5-trifluoromethoxy N-benzyl isatins. J. Med. Chem. 2009 Jun 6/11/2009; 52(11): 3445-8. PMID: 19438238, PMCID: PMC3875304, DOI: 10.1021/jm900286j, ISSN: 1520-4804.

Marlo JE, Niswender CM, Days EL, Bridges TM, Xiang Y, Rodriguez AL, Shirey JK, Brady AE, Nalywajko T, Luo Q, Austin CA, Williams MB, Kim K, Williams R, Orton D, Brown HA, Lindsley CW, Weaver CD, Conn PJ. Discovery and characterization of novel allosteric potentiators of M1 muscarinic receptors reveals multiple modes of activity. Mol. Pharmacol [print-electronic]. 2009 Mar; 75(3): 577-88. PMID: 19047481, PMCID: PMC2684909, PII: mol.108.052886, DOI: 10.1124/mol.108.052886, ISSN: 1521-0111.

Weaver CD, Sheffler DJ, Lewis LM, Bridges TM, Williams R, Nalywajko NT, Kennedy JP, Mulder MM, Jadhav S, Aldrich LA, Jones CK, Marlo JE, Niswender CM, Mock MM, Zheng F, Conn PJ, Lindsley CW. Discovery and development of a potent and highly selective small molecule muscarinic acetylcholine receptor subtype I (mAChR 1 or M1) antagonist in vitro and in vivo probe. Curr Top Med Chem. 2009; 9(13): 1217-26. PMID: 19807667, PMCID: PMC4765323, PII: CTMC-Abs-011-9-13, ISSN: 1873-4294.

Bridges TM, Williams R, Lindsley CW. Design of potent GlyT1 inhibitors: in vitro and in vivo profiles. Curr. Opin. Mol. Ther. 2008 Dec; 10(6): 591-601. PMID: 19051137, ISSN: 1464-8431.

Brady AE, Jones CK, Bridges TM, Kennedy JP, Thompson AD, Heiman JU, Breininger ML, Gentry PR, Yin H, Jadhav SB, Shirey JK, Conn PJ, Lindsley CW. Centrally active allosteric potentiators of the M4 muscarinic acetylcholine receptor reverse amphetamine-induced hyperlocomotor activity in rats. J. Pharmacol. Exp. Ther [print-electronic]. 2008 Dec; 327(3): 941-53. PMID: 18772318, PMCID: PMC2745822, PII: jpet.108.140350, DOI: 10.1124/jpet.108.140350, ISSN: 1521-0103.

Miller NR, Daniels RN, Bridges TM, Brady AE, Conn PJ, Lindsley CW. Synthesis and SAR of analogs of the M1 allosteric agonist TBPB. Part II: Amides, sulfonamides and ureas--the effect of capping the distal basic piperidine nitrogen. Bioorg. Med. Chem. Lett [print-electronic]. 2008 Oct 10/15/2008; 18(20): 5443-7. PMID: 18829311, PMCID: PMC3177607, PII: S0960-894X(08)01088-3, DOI: 10.1016/j.bmcl.2008.09.032, ISSN: 1464-3405.

Bridges TM, Brady AE, Kennedy JP, Daniels RN, Miller NR, Kim K, Breininger ML, Gentry PR, Brogan JT, Jones CK, Conn PJ, Lindsley CW. Synthesis and SAR of analogues of the M1 allosteric agonist TBPB. Part I: Exploration of alternative benzyl and privileged structure moieties. Bioorg. Med. Chem. Lett [print-electronic]. 2008 Oct 10/15/2008; 18(20): 5439-42. PMID: 18805692, PMCID: PMC3177598, PII: S0960-894X(08)01078-0, DOI: 10.1016/j.bmcl.2008.09.023, ISSN: 1464-3405.

Jones CK, Brady AE, Davis AA, Xiang Z, Bubser M, Tantawy MN, Kane AS, Bridges TM, Kennedy JP, Bradley SR, Peterson TE, Ansari MS, Baldwin RM, Kessler RM, Deutch AY, Lah JJ, Levey AI, Lindsley CW, Conn PJ. Novel selective allosteric activator of the M1 muscarinic acetylcholine receptor regulates amyloid processing and produces antipsychotic-like activity in rats. J. Neurosci. 2008 Oct 10/8/2008; 28(41): 10422-33. PMID: 18842902, PMCID: PMC2577155, PII: 28/41/10422, DOI: 10.1523/JNEUROSCI.1850-08.2008, ISSN: 1529-2401.

Bridges TM, Lindsley CW. G-protein-coupled receptors: from classical modes of modulation to allosteric mechanisms. ACS Chem. Biol [print-electronic]. 2008 Sep 9/19/2008; 3(9): 530-41. PMID: 18652471, DOI: 10.1021/cb800116f, ISSN: 1554-8937.

Kennedy JP, Williams L, Bridges TM, Daniels RN, Weaver D, Lindsley CW. Application of combinatorial chemistry science on modern drug discovery. J Comb Chem [print-electronic]. 2008 May; 10(3): 345-54. PMID: 18220367, DOI: 10.1021/cc700187t, ISSN: 1520-4774.

Lewis LM, Sheffler D, Williams R, Bridges TM, Kennedy JP, Brogan JT, Mulder MJ, Williams L, Nalywajko NT, Niswender CM, Weaver CD, Conn PJ, Lindsley CW. Synthesis and SAR of selective muscarinic acetylcholine receptor subtype 1 (M1 mAChR) antagonists. Bioorg. Med. Chem. Lett [print-electronic]. 2008 Feb 2/1/2008; 18(3): 885-90. PMID: 18178088, PMCID: PMC2275053, PII: S0960-894X(07)01510-7, DOI: 10.1016/j.bmcl.2007.12.051, ISSN: 1464-3405.

Bridges TM. Pharmaceutical aphrodisia. Curr Top Med Chem. 2007; 7(11): 1152. PMID: 17722370, ISSN: 1873-4294.