Raymond G Booth

Northeastern University, Boston, Massachusetts, United States

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Publications (54)152.35 Total impact

  • Tania C. Córdova-Sintjago, Yue Liu, Raymond G. Booth
    Molecular Physics 12/2014; · 1.64 Impact Factor
  • James M. Kasper, Raymond G. Booth, Joanna Peris
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    ABSTRACT: The serotonin 5-HT2C receptor has shown promise in vivo as a pharmacotherapeutic target for alcoholism. For example, recently, a novel 4-phenyl-2-N,N-dimethylaminotetralin (PAT) drug candidate, that demonstrates 5-HT2C receptor agonist activity together with 5-HT2A/2B receptor inverse agonist activity, was shown to reduce operant responding for ethanol after peripheral administration to rats. Previous studies have shown that the 5-HT2C receptor is found throughout the mesoaccumbens pathway and that 5-HT2C receptor agonism causes activation of ventral tegmental area (VTA) GABA neurons. It is unknown what effect 5-HT2C receptor modulation has on GABA release in the nucleus accumbens core (NAcc). To this end, microdialysis coupled to capillary electrophoresis with laser-induced fluorescence was used to quantify extracellular neurotransmitter concentrations in the NAcc under basal and after potassium stimulation conditions, in response to PAT analogs and other 5-HT2C receptor modulators administered by reverse dialysis to rats. 5-HT2C receptor agonists specifically attenuated stimulated GABA release in the NAcc while 5-HT2C antagonists or inverse agonists had no effect. Agents with activity at 5-HT2A receptors had no effect on GABA release. Thus, in contrast to results reported for the VTA, current results suggest 5-HT2C receptor agonists decrease stimulated GABA release in the NAcc, and provide a possible mechanism of action for 5HT2C-mediated negative modulation of ethanol self-administration. Synapse, 2014. © 2014 Wiley Periodicals, Inc.
    Synapse 11/2014; · 2.43 Impact Factor
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    ABSTRACT: Development of 5-HT2C agonists for treatment of neuropsychiatric disorders, including psychoses, substance abuse, and obesity, has been fraught with difficulties, because the vast majority of reported 5-HT2C selective agonists also activate 5-HT2A and/or 5-HT2B receptors, potentially causing hallucinations and/or cardiac valvulopathy. Herein is described a novel, potent, and efficacious human 5-HT2C receptor agonist, (-)-trans-(2S,4R)-4-(3'[meta]-bromophenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine ((-)-MBP), that is a competitive antagonist and inverse agonist at human 5-HT2A and 5-HT2B receptors, respectively. In three C57Bl/6 mouse models of drug-induced psychoses ([2,5]-dimethoxy-4-iodoamphetamine elicited head-twitch response, MK-801-induced hyperlocomotion, and amphetamine-induced hyperlocomotion), (-)-MBP has efficacy comparable to the prototypical second-generation antipsychotic drug, clozapine. (-)-MBP, however, does not alter locomotion when administered alone, distinguishing it from clozapine, which suppresses locomotion. Finally, consumption of highly palatable food by mice was not increased by (-)-MBP at a dose that produced at least 50% maximal efficacy in the psychoses models. Compared to (-)-MBP, (+)-MBP was much less active across in vitro affinity and functional assays using mouse and human receptors, and also translated in vivo with comparably lower potency and efficacy. Results indicate a 5-HT2C receptor-specific agonist, such as (-)-MBP, may be pharmacotherapeutic for psychoses, without liability for obesity, hallucinations, heart disease, sedation or motoric disorders.
    Journal of Pharmacology and Experimental Therapeutics 02/2014; · 3.89 Impact Factor
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    ABSTRACT: The serotonin (5-hydroxytryptamine, 5-HT) 5-HT2 G protein-coupled receptor (GPCR) family consists of types 2A, 2B, and 2C that share ~75% transmembrane (TM) sequence identity. Agonists for 5-HT2C receptors are under development for psychoses, whereas, at 5-HT2A receptors, antipsychotic effects are associated with antagonists-in fact, 5-HT2A agonists can cause hallucinations and 5-HT2B agonists cause cardiotoxicity. It is known that 5-HT2A TM6 residues W6.48, F6.51, and F6.52 impact ligand binding and function, however, ligand interactions with these residues at the 5-HT2C receptor has not been reported. To predict and validate molecular determinants for 5-HT2C-specific activation, results from receptor homology modeling, ligand docking, and molecular dynamics (MD) simulation studies were compared with experimental results for ligand binding and function at wild type and W6.48A, F6.51A, and F6.52A point-mutated 5-HT2C receptors.
    Molecular Physics 01/2014; 112(3-4):398-407. · 1.64 Impact Factor
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    ABSTRACT: During translational studies to develop trans-4-phenyl-2-dimethylaminotetralin (PAT) compounds for neuropsychiatric disorders, the (+)- and (-)-enantiomers of the analog 6-OH-7-Cl-PAT demonstrated unusual pharmacology at serotonin 5-HT2 G protein-coupled-receptors (GPCRs). The enantiomers had similar affinities (Ki) at human (h) 5-HT2A receptors (~70 nM), however, in an in vivo mouse model of 5-HT2A receptor activation ((±)-(2,5)-dimethoxy-4-iodoamphetamine elicited head-twitch), (-)-6-OH-7-Cl-PAT was about 5-fold more potent than the (+)-enantiomer. It was discovered (+)-6-OH-7-Cl-PAT (only) had ~40-fold lower affinity at mouse (m) compared to h5-HT2A receptors. Molecular modeling and computational ligand docking studies indicated the 6-OH moiety of (+)- but not (-)-6-OH-7-Cl-PAT could form a hydrogen bond with serine (S) 5.46 at the h5-HT2A receptor, however, the m5-HT2A as well as m5-HT2B, h5-HT2B, m5-HT2C, and h5-HT2C receptors have alanine (A) at position 5.46, obviating this interaction; (+)-6-OH-7-Cl-PAT also showed ~50-fold lower affinity than (-)-6-OH-7-Cl-PAT at mouse and h5-HT2C receptors. Mutagenesis studies confirmed 5-HT2A S5.46 is critical for (+)- but not (-)-6-OH-7-Cl-PAT binding, as well as function. The (+)-6-OH-7-Cl-PAT enantiomer showed partial agonist effects at h5-HT2A WT and m5-HT2A A5.46S point-mutated receptors, but did not activate m5-HT2A WT and h5-HT2A S5.46A point-mutated receptors, or h5-HT2B, h5-HT2C, and m5-HT2C receptors; (-)-6-OH-7-Cl-PAT did not activate any of the 5-HT2 receptors. Experiments also included (+) and (-)-6-OMe-7-Cl-PAT to validate hydrogen bonding interactions proposed for the corresponding 6-OH analogs. Results indicate PAT ligand 3-dimensional structure impacts target receptor binding and translational outcomes, supporting the hypothesis that GPCR ligand structure governs orthosteric binding pocket molecular determinants and resulting pharmacology.
    Journal of Pharmacology and Experimental Therapeutics 09/2013; · 3.89 Impact Factor
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    ABSTRACT: Serotonin (5-HT) 5-HT2C receptor agonists have shown promise as novel alcoholism pharmacotherapies, but developing selective agonists has been problematic. Female Sprague Dawley rats were given ethanol in a palatable gel vehicle during operant sessions. 5-HT2C receptor modulators (Ro60-0175, SB242,084, and (-)-trans-PAT) were administered before operant sessions. As a control for the effects of 5-HT2C receptor agonism on caloric intake, drugs were also tested using non-ethanol containing gelatin. Ro60-0175, a 5-HT2 family receptor agonist, decreased both ethanol and vehicle responding while (-)-trans-PAT, a 5-HT2C receptor agonist with 5-HT2A-2B receptor inverse agonist activity, selectively reduced only ethanol responding. The effect of 5-HT2C receptor agonists on self-administration after reinstatement of ethanol after a three week deprivation was also determined. (-)-trans-PAT eliminated increases in ethanol intake following ethanol deprivation whereas Ro60-0175 had no effect. These results emphasize the need for caloric controls and further support the idea that selective modulation of 5-HT2 family receptors is a potential pharmacotherapeutic approach in the treatment of alcoholism.
    European journal of pharmacology 09/2013; · 2.59 Impact Factor
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    ABSTRACT: BACKGROUND: Desired serotonin 5HT2 receptor pharmacology for treatment of psychoses is 5HT2A antagonism and/or 5HT2C agonism. No selective 5HT2A antagonist has been approved for psychosis and the only approved 5HT2C agonist (for obesity) also activates 5HT2A and 5HT2B receptors, which can lead to clinical complications. Studies herein tested the hypothesis that a dual-function 5HT2A antagonist/5HT2C agonist that does not activate 5HT2B receptors would be suitable for development as an antipsychotic drug, without liability for weight gain. METHODS: The novel compounds (+)- and (-)-trans-4-(4'-chlorophenyl)-N,N-dimethyl-2-aminotetralin (p-Cl-PAT) were synthesized, characterized in vitro for affinity and functional activity at human 5HT2 receptors, and administered by intraperitoneal (i.p.) and oral (gavage) routes to mice in behavioral paradigms that assessed antipsychotic efficacy and effects on feeding behavior. RESULTS: (+)- and (-)-p-Cl-PAT activated 5HT2C receptors, with (+)-p-Cl-PAT being 12-times more potent, consistent with its higher affinity across 5HT2 receptors. Neither p-Cl-PAT enantiomer activated 5HT2A or 5HT2B receptors at concentrations up to 300-times greater than their respective affinity (Ki), and (+)-p-Cl-PAT was shown to be a 5HT2A competitive antagonist. When administered i.p. or orally, (+)- and (-)-p-Cl-PAT attenuated the head-twitch response (HTR) in mice elicited by the 5HT2 agonist (-)-2,5-dimethoxy-4-iodoamphetamine (DOI) and reduced intake of a highly palatable food in non-food-deprived mice, with (+)-p-Cl-PAT being more potent across behavioral assays. CONCLUSIONS: The novel in vitro pharmacology of (+)-p-Cl-PAT (5HT2A antagonism/5HT2C agonism without activation of 5HT2B) translated in vivo to an orally-active drug candidate with preclinical efficacy to treat psychoses without liability for weight gain.
    Neuropharmacology 05/2013; · 4.82 Impact Factor
  • Clinton E Canal, Raymond G Booth, Drake Morgan
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    ABSTRACT: There are seemingly conflicting data in the literature regarding the role of serotonin (5-HT) 5-HT2C receptors in the mouse head-twitch response (HTR) elicited by the hallucinogenic 5-HT2A/2B/2C receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI). Namely, both 5-HT2C receptor agonists and antagonists, regarding 5-HT2C receptor-mediated Gq-phospholipase C (PLC) signaling, reportedly attenuate the HTR response. The present experiments tested the hypothesis that both classes of 5-HT2C receptor compounds could attenuate the DOI-elicited-HTR in a single strain of mice, C57Bl/6J. The expected results were considered in accordance with ligand functional selectivity. Commercially-available 5-HT2C agonists (CP-809,101, Ro 60-0175, WAY 161503, mCPP, and 1-methylpsilocin), novel 4-phenyl-2-N,N-dimethyl-aminotetralin (PAT)-type 5-HT2C agonists (with 5-HT2A/2B antagonist activity), and antagonists selective for 5-HT2A (M100907), 5-HT2C (SB-242084), and 5-HT2B/2C (SB-206553) receptors attenuated the DOI-elicited-HTR. In contrast, there were differential effects on locomotion across classes of compounds. The 5-HT2C agonists and M100907 decreased locomotion, SB-242084 increased locomotion, SB-206553 resulted in dose-dependent biphasic effects on locomotion, and the PATs did not alter locomotion. In vitro molecular pharmacology studies showed that 5-HT2C agonists potent for attenuating the DOI-elicited-HTR also reduced the efficacy of DOI to activate mouse 5-HT2C receptor-mediated PLC signaling in HEK cells. Although there were differences in affinities of a few compounds at mouse compared to human 5-HT2A or 5-HT2C receptors, all compounds tested retained their selectivity for either receptor, regardless of receptor species. Results indicate that 5-HT2C receptor agonists and antagonists attenuate the DOI-elicited-HTR in C57Bl/6J mice, and suggest that structurally diverse 5-HT2C ligands result in different 5-HT2C receptor signaling outcomes compared to DOI.
    Neuropharmacology 01/2013; · 4.82 Impact Factor
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    ABSTRACT: Ligands that activate the serotonin 5-HT2C G protein-coupled receptor (GPCR) may be therapeutic for psychoses, addiction, and other neuropsychiatric disorders. Ligands that are antagonists at the closely related 5-HT2A GPCR also may treat neuropsychiatric disorders; in contrast, 5-HT2A activation may cause hallucinations. 5-HT2C-specific agonist drug design is challenging because 5-HT2 GPCRs share 80% transmembrane (TM) homology, same second messenger signaling, and no crystal structures are reported. To help delineate molecular determinants underlying differential binding and activation of 5-HT2 GPCRs, 5-HT2A, and 5-HT2C homology models were built from the β 2-adrenergic GPCR crystal structure and equilibrated in a lipid phosphatidyl choline bilayer performing molecular dynamics simulations. Ligand docking studies at the 5-HT2 receptor models were conducted with the (2R, 4S)- and (2S, 4R)-enantiomers of the novel 5-HT2C agonist/5-HT2A/2B antagonist trans-4-phenyl-N,N-dimethyl-2-aminotetralin (PAT) and its 4'-chlorophenyl congners. Results indicate PAT-5-HT2 molecular interactions especially in TM domain V are important for the (2R, 4S) enantiomer, whereas, TM domain VI and VII interactions are more important for the (2S, 4R) enantiomer.
    International Journal of Quantum Chemistry 12/2012; 112(24):3807-3814. · 1.17 Impact Factor
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    ABSTRACT: The human histamine H 1 G-protein coupled receptor (GPCR) is an important drug target for inflammatory, sleep, and other neuropsychiatric disorders. To delineate molecular determinants for ligand binding for drug discovery purposes, human H 1 receptor models were built by homology to the crystal structure of the human β 2 adrenoceptor (β 2 AR) and from the recently reported crystal structure of the human H 1 receptor complex with doxepin at 3.1 Å (PDB code 3RZE). Ligand affinity of histamine and the H 1 antagonists mepyramine and (2S, 4R)-(–)-trans-4-phenyl-2-N, N-dimethylaminotetralin (PAT) at wild type and point-mutated (D3.32A, Y3.33A, W4.56A, F5.47A, W6.48A, Y6.51A, F6.52A, F6.55A, Y7.43A) human H 1 receptors were determined experimentally and results analyzed by ligand docking and molecular dynamic studies at WT and point-mutated H 1 receptor models. Differences in ligand binding affinities correlated to differences in ligand binding modes at models built according to homology or crystal structure, indicating, both models are accurate templates for predicting ligand affinity for H 1 drug design.
    J Chem Pharm Res. 08/2012; ISSN : 0975-7384(4(6)):2937-2951.
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    ABSTRACT: Activation of the serotonin (5-hydroxytryptamine, 5-HT) 5HT2C G protein-coupled receptor (GPCR) is proposed as novel pharmacotherapy for obesity and neuropsychiatric disorders. In contrast, activation of the 5-HT2A and 5-HT2B GPCRs is associated with untoward hallucinogenic and cardiopulmonary effects, respectively. There is no crystal structure available to guide design of 5-HT2C receptor-specific ligands. For this reason, a homology model of the 5-HT2C receptor was built based on the crystal structure of the human β 2 adrenoceptor GPCR to delineate molecular determinants of ligand-receptor interactions for drug design purposes. Computational and experimental studies were carried out to validate the model. Binding of N(CH3)2-PAT [(1R, 3S)-(-)-trans-1-phenyl-3-N,N-dimethylamino-1,2,3,4-tetrahydronaphthalene], a novel 5-HT2C agonist/5-HT2A/2B inverse agonist, and its secondary [NH(CH3)-PAT] and primary (NH2-PAT) amine analogs were studied at the 5-HT2C wild type (WT) and D3.32A, S3.36A, and Y7.43A 5-HT2C point-mutated receptors. Reference ligands included the tertiary amines lisuride and mesulergine and the primary amine 5-HT. Modeling results indicated that 5-HT2C residues D3.32, S3.36, and Y7.43 play a role in ligand binding. Experimental ligand binding results with WT and point-mutated receptors confirmed the impact of D3.32, S3.36, and Y7.43 on ligand affinity.
    International Journal of Quantum Chemistry 01/2012; 112(1). · 1.17 Impact Factor
  • 243 ACS National meeting; 01/2012
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    ABSTRACT: Specific activation of serotonin (5-HT) 5-HT(2C) G protein-coupled receptors may be therapeutic for obesity and neuropsychiatric disorders. Mutagenesis coupled with computational and molecular modeling experiments based on the human β₂ adrenergic receptor structure was employed to delineate the interactions of different ligands at human 5-HT(2C) residues D3.32, S3.36 and Y7.43. No binding of the tertiary amine radioligand ([³H]-mesulergine) could be detected when the 5-HT(2C) D3.32 residue was mutated to alanine (D3.32A). The S3.36A point-mutation greatly reduced affinity of primary amine ligands, modestly reduced affinity of a secondary amine, and except for the 5-HT(2C)-specific agonist N(CH₃)₂-PAT, affinity of tertiary amines was unaffected. Molecular modeling results indicated that the primary amines form hydrogen bonds with the S3.36 residue, whereas, with the exception of N(CH₃)₂-PAT, tertiary amines do not interact considerably with this residue. The Y7.43A point-mutation greatly reduced affinity of 5-HT, yet reduced to a lesser extent the affinity of tryptamine that lacks the 5-hydroxy moiety present in 5-HT; modeling results indicated that the 5-HT 5-hydroxy moiety hydrogen bonds with Y7.43 at the 5-HT(2C) receptor. Additional modeling results showed that 5-HT induced a hydrogen bond between Y7.43 and D3.32. Finally, modeling results revealed two low-energy binding modes for 5-HT in the 5-HT(2C) binding pocket, supporting the concept that multiple agonist binding modes may stabilize different receptor active conformations to influence signaling. Ligand potencies for modulating WT and point-mutated 5-HT(2C) receptor-mediated phospholipase C activity were in accordance with the affinity data. Ligand efficacies, however, were altered considerably by the S3.36A mutation only.
    European journal of pharmacology 12/2011; 673(1-3):1-12. · 2.59 Impact Factor
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    ABSTRACT: Autism symptoms are currently modulated by Selective Serotonin Reuptake Inhibitors (SSRIs). SSRIs slow onset of action limits their efficiency. The established synergistic activity of SSRIs and 5HT(1B/1D) autoreceptors antagonists motivated us to incorporate SSRIs and 5HT(1B/1D) antagonists in one 'hybrid' molecule. A library of virtual 'hybrid' molecules was designed using the tethering technique. A pharmacophore model was generated derived from 16 structurally diverse SSRIs (K(i)=0.013-5000 nM) and used as 3D query. Compounds with fit values (≥2) were chosen for synthesis and subsequent in vitro biological evaluation. Our pharmacophore model is a promising milestone to a class of SSRIs with dual action.
    Bioorganic & medicinal chemistry letters 11/2011; 21(22):6714-23. · 2.65 Impact Factor
  • European Journal of Pharmacology 01/2011; · 2.68 Impact Factor
  • Burger's Medicinal Chemistry, Drug Discovery and Development, 09/2010; , ISBN: 9780471266945
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    Adam S Vincek, Raymond G Booth
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    ABSTRACT: Mixed trifluoroacetyl phenylacetyl anhydride and 3-halostyrenes (fluoro, chloro, and bromo) or vinylcycloalkanes (cyclohexyl, cyclooctyl), undergo cascade Friedel-Crafts cycli-acylalkylation, enolization, and O-acylation to give 4-substituted tetralen-2-ol phenylacetates, without additional solvent in good yields. Base alcoholysis of 4-phenyltetralen-2-ol phenylacetate reveals the tetral-2-one for asymmetric transfer hydrogenation. Bromophenyltetralen-2-ol phenylacetate undergoes Suzuki coupling, and provides a short route to trans-4-phenyl-β-aminotetralin.
    Tetrahedron Letters 09/2009; 50(36):5107-5109. · 2.39 Impact Factor
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    ABSTRACT: The serotonin 5-HT(2A), 5-HT(2B), and 5-HT(2C) G protein-coupled receptors signal primarily through G alpha(q) to activate phospholipase C (PLC) and formation of inositol phosphates (IP) and diacylglycerol. The human 5-HT(2C) receptor, expressed exclusively in the central nervous system, is involved in several physiological and psychological processes. Development of 5-HT(2C) agonists that do not also activate 5-HT(2A) or 5-HT(2B) receptors is challenging because transmembrane domain identity is about 75% among 5-HT(2) subtypes. This paper reports 5-HT(2) receptor affinity and function of (1R,3S)-(-)-trans-1-phenyl-3-dimethylamino-1,2,3,4-tetrahydronaphthalene (PAT), a small molecule that produces anorexia and weight-loss after peripheral administration to mice. (-)-Trans-PAT is a stereoselective full-efficacy agonist at human 5-HT(2C) receptors, plus, it is a 5-HT(2A)/5-HT(2B) inverse agonist and competitive antagonist. The K(i) of (-)-trans-PAT at 5-HT(2A), 5-HT(2B), and 5-HT(2C) receptors is 410, 1200, and 37 nM, respectively. Functional studies measured activation of PLC/[(3)H]-IP formation in clonal cells expressing human 5-HT(2) receptors. At 5-HT(2C) receptors, (-)-trans-PAT is an agonist (EC(50) = 20 nM) comparable to serotonin in potency and efficacy. At 5-HT(2A) and 5-HT(2B) receptors, (-)-trans-PAT is an inverse agonist (IC(50) = 490 and 1,000 nM, respectively) and competitive antagonist (K(B) = 460 and 1400 nM, respectively) of serotonin. Experimental results are interpreted in light of molecular modeling studies indicating the (-)-trans-PAT protonated amine can form an ionic bond with D3.32 of 5-HT(2A) and 5-HT(2C) receptors, but, not with 5-HT(2B) receptors. In addition to probing 5-HT(2) receptor structure and function, (-)-trans-PAT is a novel lead regarding 5-HT(2C) agonist/5-HT(2A) inverse agonist drug development for obesity and neuropsychiatric disorders.
    European journal of pharmacology 05/2009; 615(1-3):1-9. · 2.59 Impact Factor
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    ABSTRACT: (1R,3S)-(-)-trans-1-phenyl-3-dimethylamino-1,2,3,4-tetrahydronaphthalene (PAT) is a novel compound that has full-efficacy agonist activity at human 5-HT2C receptors and inverse agonist/antagonist activity at 5HT2A and 5HT2B receptors. In the present paper we describe its effects on food intake in non-deprived C57BL/6 mice adapted to eating a palatable dessert meal each day. PAT showed a dose-related inhibition of food intake with a 50% inhibitory dose of 4.2 mg/kg. The dose-effect curve was similar to that obtained using WAY-161503. Abnormal behaviors were not observed by casual inspection following administration of PAT. The anorectic effect of PAT was additive with that of amphetamine. When PAT, or PAT+amphetamine, were injected 2 h before access to food, most of the anorectic activity had dissipated, indicating that PAT has a biologically effective period of about 1 h. Four daily injections of PAT were associated with some, but not complete loss of the initial anorectic effect; this differs from the rapid tolerance that has been reported to fenfluramine anorexia and suggests that different mechanism(s) are involved in the loss of anorexia.
    Pharmacology Biochemistry and Behavior 12/2008; 91(1):176-80. · 2.82 Impact Factor
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    ABSTRACT: The human histamine H1 Receptor (hH1R) belongs to the family of G-protein coupled receptors (GPCRs), an attractive and proven class of drug targets in a wide range of therapeutic areas. However, due to the low amount of available purified protein and the hydrophobic nature of GPCRs, limited structural information is available on ligand-receptor interaction especially for the transmembrane (TM) domain regions where the majority of ligand-receptor interactions occur. During the last decades, proteomic techniques have increasingly become an important tool to reveal detailed information on the individual GPCR class, including post-translational modifications and characterizations of GPCRs binding pocket. Herein, we report the successful functional production and mass spectrometric characterization of the hH1R, after baculovirus-driven and in vitro cell-free expression. Using only MALDI-ToF, sequence coverage of more than 80%, including five hydrophobic TM domains was achieved. Moreover, we have identified an asparagine residue in the hH1R protein that is subject to N-linked glycosylation. This information would be valuable for drug discovery efforts by allowing us to further study H1R-ligand interactions using histaminergic ligands that covalently bind the hH1R, and eventually revealing binding sites of hH1R and other GPCRs.
    Journal of Proteome Research 03/2008; 7(2):621-9. · 5.00 Impact Factor

Publication Stats

540 Citations
152.35 Total Impact Points


  • 2014
    • Northeastern University
      Boston, Massachusetts, United States
  • 2006–2013
    • University of Florida
      • • Department of Psychiatry
      • • Department of Medicinal Chemistry
      Lake Alfred, FL, United States
  • 1990–2010
    • Harvard Medical School
      • Department of Psychiatry
      Boston, MA, United States
  • 1991–2006
    • University of North Carolina at Chapel Hill
      • Division of Chemical Biology and Medicinal Chemistry
      North Carolina, United States
  • 2004
    • VU University Amsterdam
      • Department of Medicinal Chemistry
      Amsterdamo, North Holland, Netherlands
  • 2003
    • McLean Hospital
      Cambridge, Massachusetts, United States