NEUROPHARMACOKINETICS OF A NEW α-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLE PROPIONIC ACID (AMPA) MODULATOR, S18986 [(S)-2,3-DIHYDRO-[3,4]CYCLOPENTANO-1,2,4-BENZOTHIADIAZINE-1,1-DIOXIDE], IN THE RAT

@article{Bourasset2005NEUROPHARMACOKINETICSOA,
  title={NEUROPHARMACOKINETICS OF A NEW $\alpha$-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLE PROPIONIC ACID (AMPA) MODULATOR, S18986 [(S)-2,3-DIHYDRO-[3,4]CYCLOPENTANO-1,2,4-BENZOTHIADIAZINE-1,1-DIOXIDE], IN THE RAT},
  author={Fanchon Bourasset and Katy Bernard and Carmen Mu{\~n}oz and Patrick Genissel and Jean Michel Scherrmann},
  journal={Drug Metabolism and Disposition},
  year={2005},
  volume={33},
  pages={1137 - 1143}
}
The aim of our study was to determine the neuropharmacokinetics of S18986 [(S)-2,3-dihydro-[3,4]cyclopentano-1,2,4-benzothiadiazine-1,1-dioxide], a new positive allosteric modulator of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-type receptors, in the rat. We focused on its blood-brain barrier (BBB) uptake and on its brain intra- and extracellular fluid (bICF-bECF) partitioning. BBB transport of S18986 was measured using the in situ brain perfusion technique. bECF concentrations were… Expand
Positive allosteric modulators of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor.
TLDR
This work has shown that activation of metabotropic glutamate receptors results in modulation of neuronal excitability and transmission, and the ionotropic receptors are responsible for mediating the fast synaptic response to extracellular glutamate. Expand
Carrier-mediated processes at several rat brain interfaces determine the neuropharmacokinetics of morphine and morphine-6-beta-D-glucuronide.
TLDR
It is found that morphine distributes more easily outside bECF than M6G, and morphine accumulates into brain cells thanks to a probenecid-sensitive transporter located at the b ECF/bICF interface, whereas M 6G is trapped in bECFs thanks to transporters located atThe BBB and the bECf/CSF interface. Expand
Permeability of blood–brain barrier in macaque model of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐induced Parkinson disease
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DRUG FOCUS: S 18986: A Positive Allosteric Modulator of AMPA‐Type Glutamate Receptors Pharmacological Profile of a Novel Cognitive Enhancer
TLDR
S 18986, a new selective positive allosteric modulator of AMPA‐type glutamate receptors, increased induction and maintenance of LTP in the hippocampus as well as the expression of brain‐derived neurotrophic factor (BDNF) both in vitro and in vivo. Expand
Comparison of single vs. multiple administrations of the AMPA receptors modulator S 18986 in the object recognition task in rats
TLDR
Findings show a long‐lasting efficacy of the AMPA receptor allosteric modulator in the object recognition task despite a short half‐life in plasma and in brain (approximately 1 h). Expand
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It is shown that PKRinh has a very high brain uptake clearance which saturates with increasing concentrations, and improves knowledge about P‐gp‐mediated efflux across the blood‐brain barrier (BBB) for the development of new CNS directed drugs. Expand
The AMPA modulator S 18986 improves declarative and working memory performances in aged mice
TLDR
The memory-enhancing properties of S 18986 are confirmed and, in line with emerging data on multiple AMPA modulators, the relevance of targeting AMPA receptors in the development of new memory enhancers is highlighted. Expand
Behavioral and biological effects of chronic S18986, a positive AMPA receptor modulator, during aging
TLDR
Chronic, oral administration of S18986 increases locomotor activity and performance in a spatial memory task in aged rodents and attenuates the age-related increase in the expression of a microglial marker in the hippocampus, providing a framework for further studies of the potentially beneficial effects of AMPAR modulators on brain aging. Expand
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This brief review of neuromolecular medicine from the computational perspective provides compelling examples of how simulations can elucidate, explain, and predict the effect of chemical agonists, antagonists, and modulators in the nervous system. Expand
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