PET-characterization of [carbonyl-11C]WAY-100635 binding to 5-HT1A receptors in the primate brain

Abstract [carbonyl-11C]WAY-100635 is a new radioligand which can be used with positron emission tomography (PET) to provide high contrast delineation of human brain regions that are rich in 5-HT1A receptors. In the present PET study, the binding of [carbonyl-11C]WAY-100635 was characterized in the cynomolgus monkey brain. Pretreatment with each of the two reference compounds, WAY-100635 and 8-OH-DPAT, as well as the drugs buspirone and pindolol, induced a marked inhibition of [carbonyl-11C]WAY-100635 binding in the neocortex and the raphe nuclei. A preliminary Scatchard analysis yielded 5-HT1A receptor density values of the same order as those that have been reported in vitro. The study shows that [carbonyl-11C]WAY-100635 binds specifically to 5-HT1A receptors in the primate brain and has potential for determination of 5-HT1A receptor occupancy and density in psychiatric patients.

[1]  V. Pérez,et al.  Pindolol induces a rapid improvement of depressed patients treated with serotonin reuptake inhibitors. , 1994, Archives of general psychiatry.

[2]  A A Lammertsma,et al.  Evaluation of [O-methyl-3H]WAY-100635 as an in vivo radioligand for 5-HT1A receptors in rat brain. , 1994, European journal of pharmacology.

[3]  J. Palacios,et al.  Serotonin receptors in the human brain—III. Autoradiographic mapping of serotonin-1 receptors , 1987, Neuroscience.

[4]  G. Sedvall,et al.  Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Relation to extrapyramidal side effects. , 1992, Archives of general psychiatry.

[5]  P A Sargent,et al.  Exquisite delineation of 5-HT1A receptors in human brain with PET and [carbonyl-11 C]WAY-100635. , 1996, European journal of pharmacology.

[6]  G. Sedvall,et al.  Quantitative analysis of D2 dopamine receptor binding in the living human brain by PET. , 1986, Science.

[7]  L. Farde,et al.  Kinetic Analysis of Central [11C]Raclopride Binding to D2-Dopamine Receptors Studied by PET—A Comparison to the Equilibrium Analysis , 1989, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[8]  S. Stone-Elander,et al.  D2 dopamine receptors in neuroleptic-naive schizophrenic patients. A positron emission tomography study with [11C]raclopride. , 1990, Archives of general psychiatry.

[9]  D. Baldwin,et al.  The role of serotonin in depression and anxiety , 1995, International clinical psychopharmacology.

[10]  Y. Reilly,et al.  WAY100135: a novel, selective antagonist at presynaptic and postsynaptic 5-HT1A receptors. , 1993, European journal of pharmacology.

[11]  C. Dourish,et al.  Silent 5-HT1A receptor antagonists: utility as research tools and therapeutic agents. , 1993, Trends in pharmacological sciences.

[12]  M. Minchin,et al.  Characterisation of the Binding of [3H]WAY‐100635, a Novel 5‐Hydroxytryptamine1A Receptor Antagonist, to Rat Brain , 1995, Journal of neurochemistry.

[13]  A. S. Eison,et al.  Buspirone: review of its pharmacology and current perspectives on its mechanism of action. , 1986, The American journal of medicine.

[14]  M. Hamon,et al.  Selective in vivo labelling of brain 5-HT1A receptors by [3H]WAY 100635 in the mouse. , 1994, European journal of pharmacology.

[15]  J. Kleinman,et al.  Serotonin Uptake Sites and Serotonin Receptors Are Altered in the Limbic System of Schizophrenics , 1993, Neuropsychopharmacology.

[16]  P. Grasby,et al.  Characterization of the radioactive metabolites of the 5-HT1A receptor radioligand, [O-methyl-11C]WAY-100635, in monkey and human plasma by HPLC: comparison of the behaviour of an identified radioactive metabolite with parent radioligand in monkey using PET. , 1996, Nuclear medicine and biology.

[17]  M. Mintun,et al.  [11C]WAY 100635: a radioligand for imaging 5-HT1A receptors with positron emission tomography. , 1994, Life sciences.

[18]  S. Peroutka,et al.  Antagonism of 5-hydroxytryptamine1A (5-HT1A) receptor-mediated modulation of adenylate cyclase activity by pindolol and propranolol isomers. , 1988, Biochemical pharmacology.

[19]  H. Wikström,et al.  Autoradiographic localization of 5-HT1A receptors in the post-mortem human brain using [3H]WAY-100635 and [11C]WAY-100635 , 1997, Brain Research.

[20]  P. Blier,et al.  Effectiveness of pindolol with selected antidepressant drugs in the treatment of major depression. , 1995, Journal of clinical psychopharmacology.

[21]  S. Peroutka,et al.  Molecular biology of serotonin (5‐HT) receptors , 1994, Synapse.

[22]  A Malizia,et al.  First delineation of 5-HT1A receptors in human brain with PET and [11C]WAY-100635. , 1995, European journal of pharmacology.

[23]  G. Tunnicliff.  Molecular basis of buspirone's anxiolytic action. , 1991, Pharmacology & toxicology.

[24]  S. Paul,et al.  Preclinical Pharmacology of Buspirone Hydrochloride , 1984, Pharmacotherapy.

[25]  R. Schreiber,et al.  Neuronal circuits involved in the anxiolytic effects of the 5-HT1A receptor agonists 8-OH-DPAT ipsapirone and buspirone in the rat. , 1993, European journal of pharmacology.

[26]  S. Hjorth,et al.  Is pindolol a mixed agonist-antagonist at central serotonin (5-HT) receptors? , 1986, European journal of pharmacology.

[27]  P P Humphrey,et al.  International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin). , 1994, Pharmacological reviews.

[28]  S. Hjorth,et al.  The 5-HT1A receptor agonist, 8-OH-DPAT, preferentially activates cell body 5-HT autoreceptors in rat brain in vivo , 1988, Naunyn-Schmiedeberg's Archives of Pharmacology.

[29]  H. Berendsen,et al.  Interactions between 5-hydroxytryptamine receptor subtypes: is a disturbed receptor balance contributing to the symptomatology of depression in humans? , 1995, Pharmacology & therapeutics.

[30]  H. Meltzer,et al.  Serotonin1A receptors are increased in postmortem prefrontal cortex in schizophrenia , 1996, Brain Research.

[31]  K Wienhard,et al.  The ECAT EXACT HR: Performance of a New High Resolution Positron Scanner , 1994, Journal of computer assisted tomography.