Dose-dependent binding of AZD3783 to brain 5-HT 1B receptors in non-human primates and human subjects: a positron emission tomography study

Rationale The serotonin 5-HT1B receptor is a potential target for the pharmacologic treatment of depression. Positron emission tomography (PET) determination of 5HT1B receptor occupancy with drug candidates targeting this receptor in non-human primate and human subjects may facilitate translation of research from animal models and guide dose selection for clinical studies. AZD3783 is a recently developed, orally bioavailable 5-HT1B receptor antagonist with potential antidepressant properties. Objectives To determine the relationship between plasma concentration of AZD3783 and occupancy at primate brain 5-HT1B receptors using PET and the radioligand [ 11 C] AZ10419369. Methods PET studies with [ 11 C]AZ10419369 were per

[1]  Diansong Zhou,et al.  Preclinical Pharmacology and Pharmacokinetics of AZD3783, a Selective 5-Hydroxytryptamine 1B Receptor Antagonist , 2011, Journal of Pharmacology and Experimental Therapeutics.

[2]  J. Neumaier,et al.  Reduced ventral striatal/ventral pallidal serotonin1B receptor binding potential in major depressive disorder , 2011, Psychopharmacology.

[3]  Z. Bhagwagar,et al.  The 5-HT1B receptor: a novel target for the pathophysiology of depression. , 2009, Current drug targets.

[4]  Christer Halldin,et al.  [11C]AZ10419369: A selective 5-HT1B receptor radioligand suitable for positron emission tomography (PET). Characterization in the primate brain , 2008, NeuroImage.

[5]  J. Hagan,et al.  Characterisation of the selective 5-HT1B receptor antagonist SB-616234-A (1-[6-(cis-3,5-dimethylpiperazin-1-yl)-2,3-dihydro-5-methoxyindol-1-yl]-1-[2′-methyl-4′-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methanone hydrochloride): In vivo neurochemical and behavioural evidence of anxiolytic/antidep , 2006, Neuropharmacology.

[6]  Marc Flajolet,et al.  Alterations in 5-HT1B Receptor Function by p11 in Depression-Like States , 2006, Science.

[7]  N. Harada,et al.  Effect of fenfluramine‐induced increases in serotonin release on [18F]MPPF binding: A continuous infusion PET study in conscious monkeys , 2006, Synapse.

[8]  S. Wilson,et al.  Dizziness produced by a potent 5HT1A receptor agonist (eptapirone) is not due to postural hypotension , 2005, Psychopharmacology.

[9]  Lars-Gunnar Larsson,et al.  Pharmacology of a novel selective 5-hydroxytryptamine1B receptor antagonist, AR-A000002 , 2004, Naunyn-Schmiedeberg's Archives of Pharmacology.

[10]  T. Hudzik,et al.  P.1.016 In vivo pharmacology of AZD1134, a novel 5-HT1B antagonist , 2003, European Neuropsychopharmacology.

[11]  T J Hudzik,et al.  Behavioral Pharmacology of AR-A000002, a Novel, Selective 5-Hydroxytryptamine1B Antagonist , 2003, Journal of Pharmacology and Experimental Therapeutics.

[12]  Katarina Varnäs,et al.  Autoradiographic mapping of 5-HT1B and 5-HT1D receptors in the post mortem human brain using [3H]GR 125743 , 2001, Brain Research.

[13]  Osama Mawlawi,et al.  Imaging Human Mesolimbic Dopamine Transmission with Positron Emission Tomography: I. Accuracy and Precision of D2 Receptor Parameter Measurements in Ventral Striatum , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[14]  M Briley,et al.  The possible role of 5-HT(1B/D) receptors in psychiatric disorders and their potential as a target for therapy. , 2000, European journal of pharmacology.

[15]  S. Dursun,et al.  Selective serotonin reuptake inhibitor discontinuation syndrome: proposed diagnostic criteria. , 2000, Journal of psychiatry & neuroscience : JPN.

[16]  P. Bonaventure,et al.  Detailed mapping of serotonin 5-HT1B and 5-HT1D receptor messenger RNA and ligand binding sites in guinea-pig brain and trigeminal ganglion: clues for function , 1997, Neuroscience.

[17]  A. Lammertsma,et al.  Simplified Reference Tissue Model for PET Receptor Studies , 1996, NeuroImage.

[18]  G. Sedvall,et al.  Oral administration of NNC 756 — a placebo controlled PET study of D1-dopamine receptor occupancy and pharmacodynamics in man , 1995, Psychopharmacology.

[19]  C. Montigny,et al.  Current advances and trends in the treatment of depression. , 1994, Trends in pharmacological sciences.

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

[21]  B. O'dowd,et al.  A single amino-acid difference confers major pharmacological variation between human and rodent 5-HT1B receptors , 1992, Nature.

[22]  J. Palacios,et al.  5-HT1D binding sites in various species: similar pharmacological profile in dog, monkey, calf, guinea-pig and human brain membranes , 1992, Naunyn-Schmiedeberg's Archives of Pharmacology.

[23]  David J. Schlyer,et al.  Graphical Analysis of Reversible Radioligand Binding from Time—Activity Measurements Applied to [N-11C-Methyl]-(−)-Cocaine PET Studies in Human Subjects , 1990, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[24]  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.

[25]  C. Bohm,et al.  Automated blood sampling systems for positron emission tomography , 1988 .

[26]  G Maura,et al.  Cholinergic terminals in rat hippocampus possess 5-HT1B receptors mediating inhibition of acetylcholine release. , 1986, European journal of pharmacology.

[27]  T. Greitz,et al.  Head fixation device for reproducible position alignment in transmission CT and positron emission tomography. , 1981, Journal of computer assisted tomography.

[28]  C. Halldin,et al.  Quantitative analysis of ( 11 C)AZ10419369 binding to 5-HT 1B receptors in human brain , 2011 .

[29]  L. Farde,et al.  Short Communication Fenfluramine-Induced Serotonin Release Decreases ( 11 C)AZ10419369 Binding to 5-HT 1B -Receptors in the Primate Brain , 2010 .

[30]  Christer Halldin,et al.  PET examination of [11C]NNC 687 and [11C]NNC 756 as new radioligands for the D1-dopamine receptor , 2005, Psychopharmacology.

[31]  E. Schlicker,et al.  Identity of inhibitory presynaptic 5-hydroxytryptamine (5-HT) autoreceptors in the rat brain cortex with 5-HT1B binding sites , 2004, Naunyn-Schmiedeberg's Archives of Pharmacology.

[32]  Christer Halldin,et al.  Radioligand Disposition and Metabolism — Key Information in Early Drug Development , 1995 .

[33]  K. Zilles,et al.  Human brain atlas: For high‐resolution functional and anatomical mapping , 1994, Human brain mapping.