Development of 5‐HT1A receptor radioligands to determine receptor density and changes in endogenous 5‐HT

[18F]FCWAY and [18F]FPWAY, analogues of the high affinity 5‐HT1A receptor (5‐HT1AR) antagonist WAY100635, were evaluated in rodents as potential radiopharmaceuticals for determining 5‐HT1AR density and changes in receptor occupancy due to changes in endogenous serotonin (5‐HT) levels. The in vivo hippocampus specific binding ratio [(hippocampusuptake/cerebellumuptake)−1] of [18F]FPWAY was decreased to 32% of the ratio of [18F]FCWAY, indicating that [18F]FPWAY has lower affinity than [18F]FCWAY. The 5‐HT1AR selectivity of [18F]FPWAY was confirmed using ex vivo autoradiography studies with 5‐HT1AR knockout, heterozygous, and wildtype mice.

[1]  T Suhara,et al.  In vivo binding properties of [carbonyl‐11C]WAY‐100635: Effect of endogenous serotonin , 2001, Synapse.

[2]  A. Bianchi,et al.  Effects of anesthetics on hypoglossal nerve discharge and c‐fos expression in brainstem hypoglossal premotor neurons , 2004, The Journal of comparative neurology.

[3]  W C Eckelman,et al.  Fluoro analogs of WAY-100635 with varying pharmacokinetics properties. , 2000, Nuclear medicine and biology.

[4]  Joost Bart,et al.  PET Studies on P-glycoprotein function in the blood-brain barrier: how it affects uptake and binding of drugs within the CNS. , 2004, Current pharmaceutical design.

[5]  R Myers,et al.  Effect of 5‐HT on binding of [11C] WAY 100635 to 5‐HT1A receptors in rat brain, assessed using in vivo microdialysis and PET after fenfluramine , 2001, Synapse.

[6]  W C Eckelman,et al.  Development of fluorine-18-labeled 5-HT1A antagonists. , 1999, Journal of medicinal chemistry.

[7]  André Luxen,et al.  Effect of endogenous serotonin on the binding of the 5‐HT1A PET ligand 18F‐MPPF in the rat hippocampus: kinetic β measurements combined with microdialysis , 2002, Journal of neurochemistry.

[8]  Hideo Tsukada,et al.  Isoflurane anesthesia enhances the inhibitory effects of cocaine and GBR12909 on dopamine transporter: PET studies in combination with microdialysis in the monkey brain , 1999, Brain Research.

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

[10]  S. Garattini,et al.  Depletion and time-course of recovery of brain serotonin after repeated subcutaneous dexfenfluramine in the mouse. A comparison with the rat , 1995, Neuropharmacology.

[11]  Nora D Volkow,et al.  Effects of Endogenous Neurotransmitters on the in vivo Binding of Dopamine and 5-HT Radiotracers in Mice , 2001, Neuropsychopharmacology.

[12]  U. McCann,et al.  Dexfenfluramine and serotonin neurotoxicity: further preclinical evidence that clinical caution is indicated. , 1994, The Journal of pharmacology and experimental therapeutics.

[13]  W Vaalburg,et al.  Influence of P-glycoprotein on brain uptake of [18F]MPPF in rats. , 2000, European journal of pharmacology.

[14]  R. Rothman,et al.  Serotonin releasing agents Neurochemical, therapeutic and adverse effects , 2002, Pharmacology Biochemistry and Behavior.

[15]  C. Maggi,et al.  Suitability of urethane anesthesia for physiopharmacological investigations in various systems Part 1: General considerations , 1986, Experientia.

[16]  J. Crider,et al.  Cloned human 5‐HT1A receptor pharmacology determined using agonist binding and measurement of cAMP accumulation , 2004, The Journal of pharmacy and pharmacology.

[17]  D Comar,et al.  High-yield radiosynthesis and preliminary in vivo evaluation of p-[18F]MPPF, a fluoro analog of WAY-100635. , 1998, Nuclear medicine and biology.

[18]  H. Kung,et al.  Synthesis and evaluation of 4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p- iodobenzamido]ethyl]piperazine (p-MPPI): a new iodinated 5-HT1A ligand. , 1994, Journal of medicinal chemistry.

[19]  H. Westenberg,et al.  The effects of selective serotonin reuptake inhibitors on extracellular 5-HT in the hippocampus of 5-HT 1 B receptor knockout mice , 2002 .

[20]  A. Meneses,et al.  5-HT system and cognition , 1999, Neuroscience & Biobehavioral Reviews.

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

[22]  W. Soudijn,et al.  The concept of selectivity in 5-HT receptor research. , 1990, European journal of pharmacology.

[23]  A. Gardier,et al.  Effects of repeated systemic administration of d-Fenfluramine on serotonin and glutamate release in rat ventral hippocampus: comparison with methamphetamine using in vivo microdialysis , 2001, Naunyn-Schmiedeberg's Archives of Pharmacology.

[24]  B. Kobilka,et al.  Identification of a single amino acid residue responsible for the binding of a class of beta-adrenergic receptor antagonists to 5-hydroxytryptamine1A receptors. , 1992, Molecular pharmacology.

[25]  L. Keil,et al.  Urethane Anesthesia in Rats , 1981 .

[26]  J. Palacios,et al.  Serotonin receptors in the human brain. I. Characterization and autoradiographic localization of 5-HT1A recognition sites. Apparent absence of 5-HT1B recognition sites , 1986, Brain Research.

[27]  F. Artigas,et al.  Role of 5‐HT1A autoreceptors in the mechanism of action of serotoninergic antidepressant drugs: recent findings from in vivo microdialysis studies , 1996, Fundamental & clinical pharmacology.

[28]  N. Rowland,et al.  Neurobiology of an anorectic drug: Fenfluramine , 1986, Progress in Neurobiology.

[29]  E. Sibille,et al.  Differential effects of 5-HT1A receptor deletion upon basal and fluoxetine-evoked 5-HT concentrations as revealed by in vivo microdialysis , 2001, Brain Research.

[30]  W C Eckelman,et al.  PET evaluation of [(18)F]FCWAY, an analog of the 5-HT(1A) receptor antagonist, WAY-100635. , 2000, Nuclear medicine and biology.

[31]  D. Murphy,et al.  Modifications of the serotonergic system in mice lacking serotonin transporters: an in vivo electrophysiological study. , 2001, The Journal of pharmacology and experimental therapeutics.

[32]  P. K. Dey,et al.  Changes in blood-brain barrier and cerebral blood flow following elevation of circulating serotonin level in anesthetized rats , 1990, Brain Research.

[33]  W. Pardridge,et al.  Drug Delivery to the Brain , 1997, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[34]  C. Maggi,et al.  Suitability of urethane anesthesia for physiopharmacological investigations. Part 3: Other systems and conclusions , 1986, Experientia.

[35]  R. Hen,et al.  Altered Emotional States in Knockout Mice Lacking 5-HT1A or 5-HT1B Receptors , 1999, Neuropsychopharmacology.

[36]  Hideo Tsukada,et al.  Comparative effects of methamphetamine and nicotine on the striatal [11C]raclopride binding in unanesthetized monkeys , 2002, Synapse.

[37]  P R Saxena,et al.  Serotonin receptors: subtypes, functional responses and therapeutic relevance. , 1995, Pharmacology & therapeutics.