The role of M1 muscarinic receptor agonism of N-desmethylclozapine in the unique clinical effects of clozapine

Psychopharmacology

Volumn 177, Issue 1-2, 2004, Pages 207-216

  Weiner, D M ^a   Meltzer, H Y ^b   Veinbergs, I ^a   Donohue, E M ^a   Spalding, T A ^a   Smith, T T ^a   Mohell, N ^a   Harvey, S C ^a   Lameh, J ^a   Nash, N ^a   Vanover, K E ^a   Olsson, R ^a   Jayathilake, K ^b   Lee, M ^b   Levey, A I ^c   Hacksell, U ^a   Burstein, E S ^a   Davis, R E ^a   Brann, M R ^a  

^a ACADIA PHARMACEUTICALS INC   (United States)

^b VANDERBILT UNIVERSITY   (United States)

^c EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Agonist; Antipsychotic; Clozapine; Cognition; Muscarinic acetylcholine receptors; N desmethylclozapine; N desmethylclozapine clozapine ratios; Schizophrenia

Indexed keywords

CARBACHOL; CLOZAPINE; DRUG METABOLITE; HALOPERIDOL; MITOGEN ACTIVATED PROTEIN KINASE; MUSCARINIC AGENT; MUSCARINIC M1 RECEPTOR; N NOROLANZAPINE; NORCLOZAPINE; OLANZAPINE; RISPERIDONE; SCOPOLAMINE; UNCLASSIFIED DRUG; XANOMELINE; ZIPRASIDONE;

AGONIST; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CLINICAL ARTICLE; COGNITION; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG DETERMINATION; DRUG EFFECT; DRUG POTENCY; DRUG RECEPTOR BINDING; ENZYME ACTIVATION; HIPPOCAMPUS; HUMAN; IC 50; MENTAL PATIENT; MOUSE; NONHUMAN; PREDICTION; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; PSYCHOPHARMACOLOGY;

ANIMALS; CHO CELLS; CLOZAPINE; CRICETINAE; DOSE-RESPONSE RELATIONSHIP, DRUG; HIPPOCAMPUS; HUMANS; MICE; MICE, INBRED C57BL; MUSCARINIC AGONISTS; NIH 3T3 CELLS; RECEPTOR, MUSCARINIC M1;

EID: 19944426901     PISSN: 00333158     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00213-004-1940-5     Document Type: Article

References (48)

1. Baldessarini RJ, Frankenburg FR (1991) Clozapine: a novel antipsychotic agent. N Engl J Med 324:746-754
2. Baldessarini RJ, Centorrino F, Flood JG, Volpicelli SA, Huston-Lyons D, Cohen BM (1993) Tissue concentrations of clozapine and its metabolites in the rat. Neuropsychopharmacology 9:117-124
3. Berkeley JL, Gomeza J, Wess J, Hamilton SE, Nathanson NM, Levey AI (2001) M1 muscarinic acetylcholine receptors activate extracellular signal-regulated kinase in CA1 pyramidal neurons in mouse hippocampal slices. Mol Cell Neurosci 18:512-524
4. Bodick NC, Offen WW, Levey AI, Cutler NR, Gauthier SG, Satlin A, Shannon HE, Tollefson GD, Rasmussen K, Bymaster FP, Hurley DJ, Potter WZ, Paul SM (1997) Effects of xanomeline, a selective muscarinic receptor agonist, on cognitive function and behavioral symptoms in Alzheimer disease. Arch Neurol 54:465-473
5. Bolden C, Cusack B, Richelson E (1991) Clozapine is a potent and selective muscarinic antagonist at the five cloned human muscarinic acetylcholine receptors expressed in CHO-K1 cells. Eur J Pharmacol 192:205-206
6. Bondesson U, Lindstrom LH (1988) Determination of clozapine and its N-demethylated metabolite in plasma by use of gas chromatography-mass spectrometry with single ion detection. Psychopharmacology 95:472-475
7. Bonner TI, Buckley NJ, Young AC, Brann MR (1987) Identification of a family of muscarinic acetylcholine receptor genes. Science 237:527-532
8. Brauner-Osborne H, Ebert B, Brann MR, Falch E, Krogsgaard-Larsen P (1996) Functional partial agonism at cloned human muscarinic acetylcholine receptors. Eur J Pharmacol 313:145-150
9. Bymaster FB, Carter PA, Yamada M, Gomeza J, Wess J, Hamilton S, Nathanson NM, McKinzie DL, Felder CC (2003) Role of specific muscarinic receptor subtypes in cholinergic parasympathomimetic responses, in vivo phosphoinositide hydrolysis, and pilocarpine-induced seizure activity. Eur J Neurosci 17:1403-1410
10. Carlsson A (1978) Antipsychotic drugs, neurotransmitters, and schizophrenia. Am J Psychiatry 135(2):165-173
11. Davis RE, Emmerling MR, Jaen JC, Moos WH, Spiegel K (1993) Therapeutic intervention in dementia. Crit Rev Neurobiol 7:41-83
12. Fabrazzo M, La Pia S, Monteleone P, Esposito G, Pinto A, De Simone L, Bencivenga R, Maj M (2002) Is time course of clozapine response correlated to the time course of plasma clozapine levels? A one-year prospective study in drug-resistant patients with schizophrenia. Neuropsychopharmacology 27:1050-1055
13. Frazier JA, Glassner Cohen L, Jacobsen L, Grothe D, Flood J, Baldessarini RJ, Piscitelli S, Kim GS, Rapoport JL (2003) Clozapine pharmacokinetics in children and adolescents with childhood-onset schizophrenia. J Clin Psychopharmacol 23 (1):87-91
14. Fritze J, Elliger T (1995) Pirenzepine for clozapine-induced hypersalivation. Lancet 346:1034
15. Gauch R, Michaelis W (1971) The metabolism of 8-chloro-11-(4-methyl-1- piperazinyl)-5H-dibenzo [b,e] [1,4] diazepine (clozapine) in mice, dogs, and human subjects. Farmaco 26:667-681
16. Gerber DJ, Sotnikova TD, Gainetdinov RR, Huang SY, Caron MG, Tonegawa S (2001) Hyperactivity, elevated dopaminergic transmission, and response to amphetamine in M1 muscarinic acetylcholine receptor-deficient mice. Proc Natl Acad Sci USA 98(26): 15312-15371
17. Green MF (1996) What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry 153:321-330
18. Hagger C, Buckley P, Kenny JT, Friedman L, Ubogy D, Meltzer HY (1993) Improvement in cognitive functions and psychiatric symptoms in treatment-refractory schizophrenic patients receiving clozapine. Biol Psychiatry 34:702-712
19. Hasegawa M, Gutierrez-Esteinou R, Way L, Meltzer HY (1993) Relationship between clinical efficacy and clozapine concentrations in plasma in schizophrenia: effect of smoking. J Clin Psychopharmacol 13:383-390
20. Heinrichs DW, Hanlon TE, Carpenter WT (1984) The quality of life scale: an instrument for rating the schizophrenia deficit syndrome. Schizophr Bull 10:388-398
21. Kane J, Honigfeld G, Singer J, Meltzer H, Clozaril Collaborative Study Group (1988) Clozapine for the treatment-resistant schizophrenic. Arch Gen Psychiatry 45:789-796
22. Kuoppamaki M, Syvalahti E, Hietala J (1993) Clozapine and N-desmethylclozapine are potent 5-HT1C receptor antagonists. Eur J Pharmacol 245:179-182
23. Lee MA, Jayathilake K, Meltzer HY (1999) A comparison of the effect of clozapine with typical neuroleptics on cognitive function in neuroleptic-responsive schizophrenia. Schizophr Res 37:1-11
24. Leucht S, Wahlbeck K, Hamann J, Kissling W (2003) New generation antipsychotics versus low-potency conventional antipsychotics: a systematic review and meta-analysis. Lancet 361(9369):1581-1589
25. Mauri MC, Volonteri LS, Dell'Osso B, Regispani F, Papa P, Baldi M, Bareggi SR (2003) Predictors of clinical outcome in schizophrenic patients responding to clozapine. J Clin Psychopharmacol 23(6):660-664
26. i values. J Pharmacol Exp Ther 251:238-246
27. Meltzer HY, Alphs L, Green AI, Altamura AC, Anand R, Bertoldi A, Bourgeois M, Chouinard G, Zahur Islam M, Kane J, Krishnan R, Lindenmayer JP, Potkin S (2003) Clozapine treatment for suicidality in schizophrenia. Arch Gen Psychiatry 60:82-91
28. Miller RJ, Hiley CR (1974) Anti-muscarinic properties of neuroleptics and drug-induced Parkinsonism. Nature 248:596-597
29. Mirza NR, Peters D, Sparks RG (2003) Xanomeline and the antipsychotic potential of muscarinic receptor subtype selective agonists. CNS Drug Rev 9(2): 159-186
30. Nordin C, Alme B, Bondesson U (1995) CSF and serum concentrations of clozapine and its demethyl metabolite: a pilot study. Psychopharmacology 122:104-107
31. Olianas MC, Maullu C, Onali P (1999) Mixed agonist-antagonist properties of clozapine at different human cloned muscarinic receptor subtypes expressed in Chinese hamster ovary cells. Neuropsychopharmacology 20(3):263-270
32. Perry PJ, Miller DD, Arndt SV, Cadoret RJ (1991) Clozapine and norclozapine plasma concentrations and clinical response of treatment-refractory schizophrenic patients. Am J Psychiatry 148(2):231-135
33. Pfeiffer CC, Jenney EH (1957) The inhibition of the conditioned response and the counteraction of schizophrenia by muscarinic stimulation of the brain. Ann NY Acad Sci 66:753-764
34. Shannon HE, Bymaster FP, Calligaro DO, Greenwood B, Mitch CH, Sawyer BD, Ward JS, Wong DT, Olesen PH, Sheardown MJ, Swedberg MDB, Suzdak PD, Sauerberg P (1994) Xanomeline: a novel muscarinic receptor agonist with functional selectivity for M1 receptors. J Pharmacol Exp Ther 269(1):271-281
35. Shannon HE, Rasmussen K, Bymaster FP, Hart JC, Peters SC, Swedberg MD, Jeppesen L, Sheardown MJ, Sauerberg P, Fink-Jensen A (2000) Xanomeline, an M(1)/M(4) preferring muscarinic cholinergic receptor agonist, produces antipsychotic-like activity in rats and mice. Schizophr Res 42:249-259
36. Snyder S, Greenberg D, Yamamura HI (1974) Anti-schizophrenic drugs and brain cholinergic receptors. Affinity for muscarinic sites predicts extrapyramidal effects. Arch Gen Psychiatry 31:58-61
37. Spalding TA, Trotter C, Skjaerbaek N, Messier TL, Currier EA, Burstein ES, Li D, Hacksell U, Brann MR (2002) Discovery of an ectopic activation site on the M(1) muscarinic receptor. Mol Pharmacol 61:1297-1302
38. Spina E, Avenoso A, Facciola G, Salemi M, Scordo MG, Ancione M, Madia AG, Perucca E (2001) Relationship between plasma risperidone and 9-hydroxyrisperidone concentrations and clinical response in patients with schizophrenia. Psychopharmacology 153:238-243
39. Sur C, Mallorga PJ, Wittmann M, Jacobson MA, Pascarella D, Williams JB, Brandish PE, Pettibone DJ, Scolnick EM, Conn PJ (2003) N-desmethylclozapine, an allosteric agonist at muscarinic 1 receptor, potentiates N-methyl-D-aspartate receptor activity. Proc Natl Acad Sci USA 100(23):13674-13679
40. The Parkinson Study Group (1999) Low-dose clozapine for the treatment of drug-induced psychosis in Parkinson's Disease. N Engl J Med 340:757-763
41. Weigmann H, Hartter S, Fischer V, Dahmen N, Hiemke C (1999) Distribution of clozapine and desmethylclozapine between blood and brain in rats. Eur Neuropsychopharmacol 9:253-256
42. Weiner DM, Levey AI, Brann MR (1990) Expression of muscarinic receptor acetylcholine and dopamine receptor mRNA's in rat basal ganglia. Proc Natl Acad Sci USA 87:7050-7054
43. Weiner DM, Burstein ES, Nash N, Croston GE, Currier EA, Vanover KE, Harvey SC, Donohue E, Hansen HC, Andersson CM, Spalding TA, Gibson DFC, Krebs-Thomson K, Powell SB, Geyer MA, Hacksell U, Brann MR (2001) 5-Hydroxytryptamine 2A receptor inverse agonists as antipsychotics. J Pharmacol Exp Ther 299:268-276
44. Weissman JT, Ma J, Essex A, Gao Y, Burstein ES (2003) G-protein-coupled receptor-mediated activation of rap GTPases: characterization of a novel Gi regulated pathway. Oncogene 23 (1):241-249
45. Wellendorph P, Goodman MW, Burstein ES, Nash NR, Brann MR, Weiner DM (2002) Molecular cloning and pharmacology of functionally distinct isoforms of the human histamine H3 receptor. Neuropharmacology 42:929-940
46. Wong AH, Van Tol HH (2003) Schizophrenia: from phenomenology to neurobiology. Neurosci Biobehav Rev 27(3):269-306
47. Young CD, Meltzer HY, Deutch AY (1998) Effects of desmethylclozapine on fos protein expression in the forebrain: in vivo biological activity of the clozapine metabolite. Neuropsychopharmacology 19:99-103
48. Zorn SH, Jones SB, Ward KM, Liston DR (1994) Clozapine is a potent and selective muscarinic M4 receptor agonist. Eur J Pharmacol 269:R1-R2