Comparative Studies of the Effects of RS‐8359 and Safrazine on Monoamine Oxidase In‐vitro and In‐vivo in Mouse Brain

@article{Yokoyama1989ComparativeSO,
  title={Comparative Studies of the Effects of RS‐8359 and Safrazine on Monoamine Oxidase In‐vitro and In‐vivo in Mouse Brain},
  author={T. Yokoyama and Tomomi Karube and Nobuhisa Iwata},
  journal={Journal of Pharmacy and Pharmacology},
  year={1989},
  volume={41}
}
Abstract— The effect of RS‐8359, (±)‐4‐(4‐cyanophenyl)amino‐6,7‐dihydro‐7‐hydroxy‐5H‐cyclopenta[d]‐pyrimidine on monoamine oxidase (MAO) has been compared with a hydrazinic MAO inhibitor, safrazine (β‐piperonylisopropylhydrazine hydrochloride,) which is a MAO inhibitor used clinically. In‐vitro radiochemical determination of MAO activity showed that the IC50 of RS‐8359 was 0·52 μM for the deamination of 5‐hydroxytryptamine (5‐HT) in the mouse brain mitochondrial preparation, while… 
Species differences in enantioselective 2‐oxidations of RS‐8359, a selective and reversible MAO‐A inhibitor, and cinchona alkaloids by aldehyde oxidase
TLDR
In vitro results were in good accordance with previously reported in vivo excretion data of the 2‐keto metabolite and the non‐detectable plasma concentrations of the (S)‐enantiomer in monkeys and humans after administration of racemic RS‐8359.
Rat strain differences in stereospecific 2‐oxidation of RS‐8359, a reversible and selective MAO‐A inhibitor, by aldehyde oxidase
TLDR
No small discrepancy existed in the almost negligible catalytic activity and the fairly high expression levels of protein and mRNA in the F344/DuCrj and Slc:Wistar strain rats, but some genetic factors might possibly be one of reasons for the discrepancy.
Stereoselective pharmacokinetics of RS-8359, a selective and reversible MAO-A inhibitor, by species-dependent drug-metabolizing enzymes.
TLDR
The rapid disappearance of the (S)-enantiomer from the plasma was thought to be due to the rapid metabolism of the (+/-)-4-cyanoanilino)-5,6-dihydro-7-hydroxy-7H-cyclopenta[d]pyrimidine by different drug-metabolizing enzymes, depending on species.
Chiral inversion of RS-8359: a selective and reversible MAO-A inhibitor via oxido-reduction of keto-alcohol.
TLDR
The results suggest that the chiral inversion might occur via an enantioselectivity of consecutive two opposing reactions, oxidation and reduction of keto-alcohol group.
Enantioselective 2-hydroxylation of RS-8359, a selective and reversible MAO-A inhibitor, by cytochrome P450 in mouse and rat liver microsomes.
TLDR
The results were in fair agreement with the previously reported low plasma concentrations of the (S)-enantiomer and the high recovery of the cis-diol metabolite derived from the (R-enantiomers) in urine after oral administration of RS-8359 to mice.
Stereospecific oxidation of the (S)-enantiomer of RS-8359, a selective and reversible monoamine oxidase A (MAO-A) inhibitor, by aldehyde oxidase
TLDR
The results suggest that the enzyme responsible for the biotransformation of RS-8359 to give the 2-keto derivative is aldehyde oxidase (EC 1.2.3.1).
Genetic Polymorphism of Aldehyde Oxidase in Donryu Rats
TLDR
Analysis of nucleotide sequences showed four substitutions, of which the substitutions at 377G>A and 2604C>T caused 110Gly-Ser and 852Ala-Val amino acid changes, respectively, which may be primarily responsible for the variations of aldehyde oxidase activity observed in Donryu rats.
Novel monoamine oxidase inhibitors, 3-(2-aminoethoxy)-1,2-benzisoxazole derivatives, and their differential reversibility.
TLDR
Subtype selectivity and reversibility of a series of novel MAO inhibitors, 3-(2-aminoethoxy)-1,2-benzisoxazole derivatives, were studied and indicate that optimization of the balance of actions can be achieved by differentiating reversibility to each target molecule.
Structural Determination of Rat and Dog Urinary Metabolites of a New Antidepressant RS-8359
RS-8359 is a selective and reversible inhibitor of A type monoamine oxidase. In order to elucidate the metabolism of RS-8359, the metabolites were isolated from the urine after oral administration to
Deamination of norepinephrine, dopamine, and serotonin by type A monoamine oxidase in discrete regions of the rat brain and inhibition by RS-8359.
TLDR
NE, DA, and 5HT are exclusively or preferentially deaminated by MAO-A in the cortex, hippocampus, and striatum of rats, and RS-8359 exhibits a reversible MAO -A inhibitory action in all three regions tested in vivo.
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