Effect of Tris (Hydroxymethyl) Aminomethane on Amine Oxidase Activity in Dog Brain, Liver and Serum and in Human Placenta

Hayashi, N; Kinemuchi, Hiroyasu; Kamijo, Keita

doi:10.1016/s0021-5198(19)52794-9

Cited by 2 publications

(2 citation statements)

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“…According to the conventional method (Hayashi et al, 1981) The radioactive products were extracted using an organic solvent (diethyl ether for MAO-A, toluene for MAO-B, and ethyl acetate for COMT), followed by measurement using a liquid scintillation counter.…”

Section: Inhibitory Effects On Enzymes Related To the Metabolism Of D...mentioning

confidence: 99%

In Vitro Pharmacological Profile of KW-6356, a Novel Adenosine A_2AReceptor Antagonist/Inverse Agonist

et al. 2023

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KW-6356 is a novel adenosine A 2A receptor (A 2A receptor) antagonist/inverse agonist, and its efficacy as monotherapy in Parkinson's disease (PD) patients has been reported. Istradefylline is a first-generation A 2A receptor antagonist approved for use as adjunct treatment to levodopa/decarboxylase inhibitor in adult PD patients experiencing OFF episodes. In this study, we investigated the in vitro pharmacological profile of KW-6356 as an A 2A receptor antagonist/inverse agonist and the mode of antagonism and compared them with istradefylline. In addition, we determined co-crystal structures of A 2A receptor in complex with KW-6356 and istradefylline to explore the structural basis of the antagonistic properties of KW-6356. Pharmacological studies have shown that KW-6356 is a potent and selective ligand for the A 2A receptor (the −log of inhibition constant = 9.93 ± 0.01 for human receptor) with a very low dissociation rate from the receptor (the dissociation kinetic rate constant = 0.016 ± 0.006 min -1 for human receptor). In particular, in vitro functional studies indicated that KW-6356 exhibits insurmountable antagonism and inverse agonism, while istradefylline exhibits surmountable antagonism. Crystallography of KW-6356-and istradefylline-bound A 2A receptor have indicated that interactions with His250 6.52 and Trp246 6.48 are essential for the inverse agonism, while the interactions at both deep inside the orthosteric pocket and the pocket lid stabilizing the extracellular loop conformation may contribute to the insurmountable antagonism of KW-6356. These profiles may reflect important difference in vivo and help predict better clinical performance.

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Section: Inhibitory Effects On Enzymes Related To the Metabolism Of D...mentioning

confidence: 99%

In Vitro Pharmacological Profile of KW-6356, a Novel Adenosine A_2AReceptor Antagonist/Inverse Agonist

et al. 2023

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“…THAM has several applications in physiology, biology, medicine, and biochemistry [Bubb et al, 1995]. It is widely used biochemically as a buffer for several biochemical processes [Brignac & Mo, 1975;Hayashi et al, 1981;Lundblad & Macdonald, 2010;Albishri & Marwani, 2016;El-Dissouky et al, 2020] and used clinically to reverse acidosis [Murakami et al, 2016;Kallet et al, 2000;Weber et al, 2000;Nahas et al, 1998]. Several THAM Schiff base derivatives showed a broad spectrum of biological activity, like anti-inflammatory, antifungal, antihistamine, anticancer, and anti-tumor effects.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and structural characterizations of tris(hydroxymethyl)aminomethane complexes with group IIA metals

Albedair¹

2021

KJS publishes peer-review articles in Mathematics, Computer Sci

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Herein, this article aimed to investigate the tendency of tris(hydroxymethyl) aminomethane (THAM) to form stable complexes with group IIA metals. Four new colorless solid complexes of group IIA metals [Ba(II), Ca(II), Sr(II) and Mg(II)] with THAM were prepared and well characterized. The chemical reactions between group IIA metals and THAM were conducted by stoichiometry of 2:1 (Ligand: Metal ion) at 65 °C and pH of ~ 8.5. Under these conditions, the THAM molecule (C4H11NO3) was deprotonated and converted to the (C4H10NO3-; L-) chelate with the metal ions. The structures of these complexes were suggested by UV-visible, IR, Raman and 1H NMR spectroscopies and other physicochemical and analytical methods (elemental analysis, thermogravimetry, and SEM). The results shows that the general composition of the complexes obtained with Ba(II), Ca(II), Sr(II) and Mg(II) ions are [BaL2(H2O)2], [CaL2(H2O)2]·2H2O, [SrL2(H2O)2], and [MgL2(H2O)2]·4H2O, respectively, and in all complexes, the geometry was octahedral.

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Effect of Tris (Hydroxymethyl) Aminomethane on Amine Oxidase Activity in Dog Brain, Liver and Serum and in Human Placenta

Cited by 2 publications

References 25 publications

In Vitro Pharmacological Profile of KW-6356, a Novel Adenosine A_2AReceptor Antagonist/Inverse Agonist

In Vitro Pharmacological Profile of KW-6356, a Novel Adenosine A_2AReceptor Antagonist/Inverse Agonist

Synthesis and structural characterizations of tris(hydroxymethyl)aminomethane complexes with group IIA metals

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Effect of Tris (Hydroxymethyl) Aminomethane on Amine Oxidase Activity in Dog Brain, Liver and Serum and in Human Placenta

Cited by 2 publications

References 25 publications

In Vitro Pharmacological Profile of KW-6356, a Novel Adenosine A2AReceptor Antagonist/Inverse Agonist

In Vitro Pharmacological Profile of KW-6356, a Novel Adenosine A2AReceptor Antagonist/Inverse Agonist

Synthesis and structural characterizations of tris(hydroxymethyl)aminomethane complexes with group IIA metals

Contact Info

Product

Resources

About

In Vitro Pharmacological Profile of KW-6356, a Novel Adenosine A_2AReceptor Antagonist/Inverse Agonist

In Vitro Pharmacological Profile of KW-6356, a Novel Adenosine A_2AReceptor Antagonist/Inverse Agonist