Muscarinic agonists with antipsychotic-like activity: Structure-activity relationships of 1,2,5-thiadiazole analogues with functional dopamine antagonist activity

Journal of Medicinal Chemistry

Volumn 41, Issue 22, 1998, Pages 4378-4384

  Sauerberg, Per ^a   Jeppesen, Lone ^a   Olesen, Preben H ^a   Rasmussen, Thøger ^a   Swedberg, Michael D B ^a   Sheardown, Malcolm J ^a   Fink Jensen, Anders ^a   Thomsen, Christian ^a   Thøgersen, Henning ^a   Rimvall, Karin ^a   Ward, John S ^b   Calligaro, David O ^b   DeLapp, Neil W ^b   Bymaster, Frank P ^b   Shannon, Harlan E ^b  

^a NOVO NORDISK A S   (Denmark)

^b ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

6 (3 BUTYLTHIO 1,2,5 THIADIAZOL 4 YL) 1 AZABICYCLO[3.2.1]OCTANE TARTRATE; 6 (3 PROPYLTHIO 1,2,5 THIADIAZOL 4 YL) 1 AZABICYCLO[3.2.1]OCTANE; DOPAMINE RECEPTOR BLOCKING AGENT; MUSCARINIC AGENT; NEUROLEPTIC AGENT; OXOTREMORINE; PILOCARPINE; THIADIAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; AVOIDANCE BEHAVIOR; DOSE RESPONSE; DRUG EFFICACY; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; EXTRAPYRAMIDAL SYMPTOM; MOUSE; NONHUMAN; PSYCHOSIS; RAT; SCHIZOPHRENIA; STRUCTURE ACTIVITY RELATION; SUBCUTANEOUS DRUG ADMINISTRATION;

EID: 15144344046     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm981048e     Document Type: Article

References (21)

1. Seeman, P.; Lee, T.; Chau-Wong, M.; Wong, K. P. Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature 1976, 261, 717-719.
2. Kane, J.; Honigfeld, G.; Singer, J.; Meltzer, H. Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch. Gen. Psych. 1988, 45, 789-719.
3. Kane, J.; Mayerhoff, D. Do negative symptoms respond to pharmacological treatment? Br. J. Psych. Suppl. 1989, 155, 115-118.
4. Arnt, J.; Skarsfeldt, T. Do novel antipsychotics have similar pharmacological characteristics? A review of evidence. Neuropsychopharmacology 1998, 18 (2), 63-101.
5. Weiner, D. M.; Levey, A. I.; Brann, M. R. Expression of muscarinic acetylcholine and dopamine receptor mRNAs in rat basal ganglia. Proc. Nail. Acad. Sci. U.S.A. 1990, 57, 7050-7054.
6. Bernard, V.; Normand, E.; Bloch, B. Phenotypical characterization of the rat striatal neurons expressing muscarinic receptor genes. J. Neurosci. 1992, 12, 3591-3600.
7. Karson, C. N.; Garcia-Rill, E.; Biederman, J.; Mrak, R. E.; Husain, M. M.; Skinner, R. D. The brain stem reticular formation in schizophrenia. Psych. Res. - Neuroimag. 1991, 40, 31-48.
8. Haroutunian, V.; Davidson, M.; Kanof, P. D.; Perl, D. P.; Powchik, P.; Losonczy, M.; McCrystal, J.; Purohit, D. P.; Bierer, L. M.; Davis, K. L. Cortical cholinergic markers in schizophrenia. Schizophrenia Res. 1994, 12, 137-144.
9. Pfeiffer, C. C.; Jenney, E. H. The inhibition of the conditioned response and the counteraction of schizophrenia by muscarinic stimulation of the brain. Ann. N. Y. Acad. Sci. 1957, 66, 653-664.
10. Bodick, N. C.; Offen, W.; Levey, A. I.; Cutler, N. R.; Gauthier, S. G.; Satlin, A.; Shannon, H. E.; Tollufson, G. D.; Rasmussen, K.; Bymaster, F. P.; Hurley, D. J.; Potter, W. Z.; Paul, S. M. Effects of Xanomeline, a Selective Muscarinic Receptor Agonist, on Cognitive Function and Behavioral Symptoms in Alzheimer Disease. Arch. Neurol. 1997, 54, 465-473.
11. Arnt, J. Pharmacological specificity of conditioned avoidance response inhibition in rats: Inhibition by neuroleptics and correlation to dopamine receptor blockade. Acta Pharmacol. Toxicol. 1982, 51, 321-329.
12. Moore, N. A.; Axton, M. S. Production of climbing behaviour in mice requires both D1 and D2 receptor activation. Psychopharmacology 1988, 94, 263-266.
13. Sauerberg, P.; Olesen, P. H.; Nielsen, S.; Treppendahl, S.; Sheardown, M. J.; Honoré, T.; Mitch, C. H.; Ward, J. S.; Pike, A. J.; Bymaster, F. P.; Sawyer, B. D.; Shannon, H. E. Novel Functional M1 Selective Muscarinic Agonists. Synthesis and Structure-Activity Relationships of 3-(1,2,5-thiadiazolyl)-1,2,5,6-tetrahydro-1-methylpyridines J. Med. Chem. 1992, 35, 2274-2283.
14. Olesen, P. H.; Sauerberg, P.; Treppendahl S.; Larsson, O.; Sheardown, M. J.; Suzdak, P. D.; Mitch, C. H.; Ward, J. S.; Bymaster, F. P.; Shannon, H. E.; Swedberg, M. D. B. 3-(3-Alkylthio-1,2,5-thiadiazol-4-yl)-1-Azabicycles. Structure-Activity Relationships For Antinociception Mediated By Central Muscarinic Receptors. Eur. J. Med. Chem. 1998, 31 (3), 221-230.
15. Olesen, P. H.; Sauerberg, P.; Petersen, T. G.; Treppendahl, S.; Bentzen, B.; Deeter, J.; Ward, J. S.; Mitch, C. H.; Lehmann, S. V. Synthesis and structural determination of stereoisomers of muscarinic ligands of the (3-propylthio-1,2,5-thiadiazol-4-yl)-1-azabicycloalkane type. Chirality 1997, 9 (8), 739-749.
16. Jones, S. V. P.; Lewvey, A. I.; Weiner, D. M. Muscarinic acetylcholine receptors. Molecular biology of G-protein-coupled receptors; Birkhauser: Boston, 1992; pp 170-197.
17. Richards, M.; van Giersberger, P. L. M. Human muscarinic receptors expressed in A9 L and CHO cells: activiation by full and partial agonists. Br. J. Pharmacol. 1995, 114, 1241-1249.
18. Ward, J. S.; Merritt, L.; Callogaro, D. O.; Bymaster, F. P.; Shannon, H. E.; Mitch, C. H.; Whitesitt, C.; Brunsting, D.; Sheardown, M. J.; Olesen, P. H.; Swedberg, M. D. B.; Jeppesen, L.; Sauerberg, P. 1,2,5-Thiadiazole Analogues of Aceclidine as Potent ml Muscarinic Agonists. J. Med. Chem. 1998, 41, 379-392.
19. Sauerberg, P.; Olesen, P. H.; Sheardown, M. J.; Rimvall, K.; Thøgersen, H.; Shannon, H. E.; Sawyer, B. D.; Ward, J. S., Bymaster, F. B.; DeLapp, N. W.; Calligaro, D. O.; Swedberg, M. D. B. Conformationally Constrained Analogues of the Muscarinic Agonist 3-(4-methylthio-1,2,5-thiadiazol-3-yl)-1,2,5,6-tetrahydro-1-methylpyridine. Synthesis, Receptor Affinity and Antinuciceptive Activity. J. Med. Chem. 1998, 41, 109-116.
20. Bymaster, F. P.; Shannon, H. E.; Rasmussen, K.; Delapp, N. W.; Mitch, C. H.; Ward, J. S.; Calligaro, D. O.; Ludvigsen, T. S.; Sheardown, M. J.; Olesen, P. H.; Swedberg, M. D. B.; Sauerberg, P.; Fink-Jensen, A. Unexpected antipsychotic-like activity with the muscarinic receptor ligand (5R,6R) 6-(3-propylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[3.2.1]octane. Eur. J. Pharmacol. 1998, 356 (2-3), 109-119.
21. Mitch, C. H.; Brown, T. J.; Bymaster, F. P.; Calligaro, D. O.; Dieckman, D.; Merrit, L.; Peters, S. C.; Quimby, S. J.; Shannon, H. E.; Shipley, L. A.; Ward, J. S.; Hansen, K.; Olesen, P. H.; Sauerberg, P.; Sheardown, M. J.; Swedberg, M. D. B.; Suzdak, P.; Greenwood, B. Muscarinic Analgesics with Potent and Selective Effects on the Gastrointestinal Tract: Potential Application for the Treatment of Irritable Bowel Syndrome. J. Med. Chem. 1997, 40, 538-546.