The Experts below are selected from a list of 102 Experts worldwide ranked by ideXlab platform
Carol L Szumlanski - One of the best experts on this subject based on the ideXlab platform.
-
methylation pharmacogenetics catechol o methyltransferase thiopurine methyltransferase and Histamine n methyltransferase
Annual Review of Pharmacology and Toxicology, 1999Co-Authors: Richard M. Weinshilboum, Diane M. Otterness, Carol L SzumlanskiAbstract:▪ Abstract Methyl conjugation is an important pathway in the biotransformation of many exogenous and endogenous compounds. Pharmacogenetic studies of methyltransferase enzymes have resulted in the identification and characterization of functionally important common genetic polymorphisms for catechol O-methyltransferase, thiopurine methyltransferase, and Histamine N-Methyltransferase. In recent years, characterization of these genetic polymorphisms has been extended to include the cloning of cDNAs and genes, as well as a determination of the molecular basis for the effects of inheritance on these methyltransferase enzymes. The thiopurine methyltransferase genetic polymorphism is responsible for clinically significant individual variations in the toxicity and therapeutic efficacy of thiopurine drugs such as 6-mercaptopurine. Phenotyping for the thiopurine methyltransferase genetic polymorphism represents one of the first examples in which testing for a pharmacogenetic variant has entered standard clinical p...
-
methylation pharmacogenetics catechol o methyltransferase thiopurine methyltransferase and Histamine n methyltransferase
Annual Review of Pharmacology and Toxicology, 1999Co-Authors: Richard M. Weinshilboum, Diane M. Otterness, Carol L SzumlanskiAbstract:Methyl conjugation is an important pathway in the biotransformation of many exogenous and endogenous compounds. Pharmacogenetic studies of methyltransferase enzymes have resulted in the identification and characterization of functionally important common genetic polymorphisms for catechol O-methyltransferase, thiopurine methyltransferase, and Histamine N-Methyltransferase. In recent years, characterization of these genetic polymorphisms has been extended to include the cloning of cDNAs and genes, as well as a determination of the molecular basis for the effects of inheritance on these methyltransferase enzymes. The thiopurine methyltransferase genetic polymorphism is responsible for clinically significant individual variations in the toxicity and therapeutic efficacy of thiopurine drugs such as 6-mercaptopurine. Phenotyping for the thiopurine methyltransferase genetic polymorphism represents one of the first examples in which testing for a pharmacogenetic variant has entered standard clinical practice. The full functional implications of pharmacogenetic variation in the activities of catechol O-methyltransferase and Histamine N-Methyltransferase remain to be determined. Finally, experimental strategies used to study methylation pharmacogenetics illustrate the rapid evolution of biochemical, pharmacologic, molecular, and genomic approaches that have been used to determine the role of inheritance in variation in drug metabolism, effect, and toxicity.
Holger Stark - One of the best experts on this subject based on the ideXlab platform.
-
procognitive properties of drugs with single and multitargeting h3 receptor antagonist activities
CNS Neuroscience & Therapeutics, 2014Co-Authors: Katarina Nikolic, Slavica Filipic, Danica Agbaba, Holger StarkAbstract:Summary The Histamine H3 receptor (H3R) is an important modulator of numerous central control mechanisms. Novel lead optimizations for H3R antagonists/inverse agonists involved studies of structure–activity relationships, cross-affinities, and pharmacokinetic properties of promising ligands. Blockade of inhibitory Histamine H3 autoreceptors reinforces Histaminergic transmission, while antagonism of H3 heteroreceptors accelerates the corticolimbic liberation of acetylcholine, norepinephrine, glutamate, dopamine, serotonin and gamma-aminobutyric acid (GABA). The H3R positioned at numerous neurotransmission crossroads indicates therapeutic applications of small-molecule H3R modulators in a number of psychiatric and neurodegenerative diseases with various clinical candidates available. Dual target drugs displaying H3R antagonism/inverse agonism with inhibition of acetylcholine esterase (AChE), Histamine N-Methyltransferase (HMT), or serotonin transporter (SERT) are novel class of procognitive agents. Main chemical diversities, pharmacophores, and pharmacological profiles of procognitive agents acting as H3R antagonists/inverse agonists and dual H3R antagonists/inverse agonists with inhibiting activity on AChE, HMT, or SERT are highlighted here.
-
bioavailability antinociceptive and antiinflammatory properties of bp 2 94 a Histamine h3 receptor agonist prodrug
Journal of Pharmacology and Experimental Therapeutics, 1997Co-Authors: A Rouleau, Holger Stark, Monique Garbarg, Xavier Ligneau, C Mantion, P Lavie, C Advenier, Jeannemarie Lecomte, M Krause, Walter SchunackAbstract:(R) α-MethylHistamine [ (R) α-MeHA], a potent and selective Histamine H3 receptor agonist in vitro and in vivo in rodents, was found to display comparatively low plasma level in healthy human volunteers, attributable to an extensive methylation of the drug’s imidazole ring by Histamine-N-Methyltransferase. To limit this inactivation process, BP 2-94, i.e., (R) -(-)-2-[[N-[1-(1 H -imidazol-4-yl)-2-propyl]imino]phenylmethyl] phenol, was selected as a prodrug. A sensitive radioimmunoassay was developed to study the generation of (R) α-MeHA slowly released from BP 2-94 in vitro and in vivo by chemical hydrolysis. In mice after oral administration of BP 2-94 high levels of both prodrug and (R) α-MeHA were detected in plasma and various tissues except in the brain. In humans receiving 0.1 mmol BP 2-94 orally, plasma levels of (R) α-MeHA-like immunoreactivity decayed with a t1/2 more than 24 hr, the area under the curve being two orders of magnitude higher than after oral administration of (R)α-MeHA. BP 2-94 displayed antiinflammatory and antinociceptive properties in rodents, related to the H3receptor stimulation. It dose-dependently inhibited capsaicin-induced plasma protein extravasation in many rat tissues with ED50s of 0.6 to 14 μmol/kg p.o., and maximal reductions by 35 to 87%. BP 2-94 also reduced zymosan-induced paw swelling in mice with an ED50 of 1 μmol/kg p.o. and showed marked activity in the phenylbenzoquinone-induced writhing (ED50 = 0.03 μmol/kg, p.o.) or formalin tests in mice, but not in the hot plate jump test. From its pharmacokinetics and pharmacological profile BP 2-94 appears to be a promising novel therapeutic agent in disorders such as asthma, migraine or a variety of inflammatory diseases and pain associated with these disorders.
Richard M. Weinshilboum - One of the best experts on this subject based on the ideXlab platform.
-
methylation pharmacogenetics catechol o methyltransferase thiopurine methyltransferase and Histamine n methyltransferase
Annual Review of Pharmacology and Toxicology, 1999Co-Authors: Richard M. Weinshilboum, Diane M. Otterness, Carol L SzumlanskiAbstract:▪ Abstract Methyl conjugation is an important pathway in the biotransformation of many exogenous and endogenous compounds. Pharmacogenetic studies of methyltransferase enzymes have resulted in the identification and characterization of functionally important common genetic polymorphisms for catechol O-methyltransferase, thiopurine methyltransferase, and Histamine N-Methyltransferase. In recent years, characterization of these genetic polymorphisms has been extended to include the cloning of cDNAs and genes, as well as a determination of the molecular basis for the effects of inheritance on these methyltransferase enzymes. The thiopurine methyltransferase genetic polymorphism is responsible for clinically significant individual variations in the toxicity and therapeutic efficacy of thiopurine drugs such as 6-mercaptopurine. Phenotyping for the thiopurine methyltransferase genetic polymorphism represents one of the first examples in which testing for a pharmacogenetic variant has entered standard clinical p...
-
methylation pharmacogenetics catechol o methyltransferase thiopurine methyltransferase and Histamine n methyltransferase
Annual Review of Pharmacology and Toxicology, 1999Co-Authors: Richard M. Weinshilboum, Diane M. Otterness, Carol L SzumlanskiAbstract:Methyl conjugation is an important pathway in the biotransformation of many exogenous and endogenous compounds. Pharmacogenetic studies of methyltransferase enzymes have resulted in the identification and characterization of functionally important common genetic polymorphisms for catechol O-methyltransferase, thiopurine methyltransferase, and Histamine N-Methyltransferase. In recent years, characterization of these genetic polymorphisms has been extended to include the cloning of cDNAs and genes, as well as a determination of the molecular basis for the effects of inheritance on these methyltransferase enzymes. The thiopurine methyltransferase genetic polymorphism is responsible for clinically significant individual variations in the toxicity and therapeutic efficacy of thiopurine drugs such as 6-mercaptopurine. Phenotyping for the thiopurine methyltransferase genetic polymorphism represents one of the first examples in which testing for a pharmacogenetic variant has entered standard clinical practice. The full functional implications of pharmacogenetic variation in the activities of catechol O-methyltransferase and Histamine N-Methyltransferase remain to be determined. Finally, experimental strategies used to study methylation pharmacogenetics illustrate the rapid evolution of biochemical, pharmacologic, molecular, and genomic approaches that have been used to determine the role of inheritance in variation in drug metabolism, effect, and toxicity.
Cinzia Volonte - One of the best experts on this subject based on the ideXlab platform.
-
Histamine regulates the inflammatory profile of sod1 g93a microglia and the Histaminergic system is dysregulated in amyotrophic lateral sclerosis
Frontiers in Immunology, 2017Co-Authors: Savina Apolloni, Paola Fabbrizio, Susanna Amadio, Giulia Napoli, Veronica Verdile, Giovanna Morello, Rosario Iemmolo, Eleonora Aronica, Sebastiano Cavallaro, Cinzia VolonteAbstract:ABSTRACT Amyotrophic Lateral Sclerosis (ALS) is a late-onset motor neuron disease where activated glia release pro-inflammatory cytokines that trigger a vicious cycle of neurodegeneration in the absence of resolution of inflammation. Given the well-established role of Histamine as a neuron-to-glia alarm signal implicated in brain disorders, the aim of this study was to investigate the expression and regulation of the Histaminergic pathway in microglial activation in ALS mouse model and in humans. By examining the contribution of the Histaminergic system to ALS, we found that particularly via H1 and H4 receptors, Histamine promoted an anti-inflammatory profile in microglia from SOD1-G93A mice and modulated their activation state. A decrease in NF-B and NADPH oxidase 2 with an increase in arginase 1 and P2Y12 receptor was induced by Histamine only in the ALS inflammatory environment, but not in the healthy microglia, together with an increase in IL-6, IL-10, CD163 and CD206 phenotypic markers in SOD1-G93A cells. Moreover, Histaminergic H1, H2, H3 and H4 receptors, and Histamine metabolizing enzymes histidine decarboxylase, Histamine N-Methyltransferase and diamine oxidase were found deregulated in spinal cord, cortex and hypothalamus of SOD1-G93A mice during disease progression. Finally, by performing a meta-analysis study, we found a modulated expression of Histamine-related genes in cortex and spinal cord from sporadic ALS patients. Our findings disclose that Histamine acts as anti-inflammatory agent in microglia and suggest a dysregulation of the Histaminergic signaling in ALS.
Diane M. Otterness - One of the best experts on this subject based on the ideXlab platform.
-
methylation pharmacogenetics catechol o methyltransferase thiopurine methyltransferase and Histamine n methyltransferase
Annual Review of Pharmacology and Toxicology, 1999Co-Authors: Richard M. Weinshilboum, Diane M. Otterness, Carol L SzumlanskiAbstract:▪ Abstract Methyl conjugation is an important pathway in the biotransformation of many exogenous and endogenous compounds. Pharmacogenetic studies of methyltransferase enzymes have resulted in the identification and characterization of functionally important common genetic polymorphisms for catechol O-methyltransferase, thiopurine methyltransferase, and Histamine N-Methyltransferase. In recent years, characterization of these genetic polymorphisms has been extended to include the cloning of cDNAs and genes, as well as a determination of the molecular basis for the effects of inheritance on these methyltransferase enzymes. The thiopurine methyltransferase genetic polymorphism is responsible for clinically significant individual variations in the toxicity and therapeutic efficacy of thiopurine drugs such as 6-mercaptopurine. Phenotyping for the thiopurine methyltransferase genetic polymorphism represents one of the first examples in which testing for a pharmacogenetic variant has entered standard clinical p...
-
methylation pharmacogenetics catechol o methyltransferase thiopurine methyltransferase and Histamine n methyltransferase
Annual Review of Pharmacology and Toxicology, 1999Co-Authors: Richard M. Weinshilboum, Diane M. Otterness, Carol L SzumlanskiAbstract:Methyl conjugation is an important pathway in the biotransformation of many exogenous and endogenous compounds. Pharmacogenetic studies of methyltransferase enzymes have resulted in the identification and characterization of functionally important common genetic polymorphisms for catechol O-methyltransferase, thiopurine methyltransferase, and Histamine N-Methyltransferase. In recent years, characterization of these genetic polymorphisms has been extended to include the cloning of cDNAs and genes, as well as a determination of the molecular basis for the effects of inheritance on these methyltransferase enzymes. The thiopurine methyltransferase genetic polymorphism is responsible for clinically significant individual variations in the toxicity and therapeutic efficacy of thiopurine drugs such as 6-mercaptopurine. Phenotyping for the thiopurine methyltransferase genetic polymorphism represents one of the first examples in which testing for a pharmacogenetic variant has entered standard clinical practice. The full functional implications of pharmacogenetic variation in the activities of catechol O-methyltransferase and Histamine N-Methyltransferase remain to be determined. Finally, experimental strategies used to study methylation pharmacogenetics illustrate the rapid evolution of biochemical, pharmacologic, molecular, and genomic approaches that have been used to determine the role of inheritance in variation in drug metabolism, effect, and toxicity.