Metabolism, excretion, and pharmacokinetics of (3-{[4-tert-butyl-benzyl)-(pyridine-3-sulfonyl)-amino]-methyl}-phenoxy)-acetic acid, an EP2 receptor-selective prostaglandin E2 agonist, in male and female Sprague-Dawley rats.

Metabolism, Excretion and Pharmacokinetics of (3-{[4-tert- Butyl-benzyl)-(pyridine-3-sulfonyl)-amino]-methyl}-phenoxy)- Acetic Acid, an Ep-2 Receptor Selective Pge2 Agonist, in Male and Female Sprague-dawley Rats Kim a Johnson and Chandra Prakash

CYP2C8- and CYP3A-mediated C-demethylation of (3-{[(4-tert-butylbenzyl)-(pyridine-3-sulfonyl)-amino]-methyl}-phenoxy)-acetic acid (CP-533,536), an EP2 receptor-selective prostaglandin E2 agonist: characterization of metabolites by high-resolution liquid chromatography-tandem mass spectrometry and liquid chromatography/mass spectrometry-nuclear magnetic resonance.

CP-533,536, (3-{[(4-tert-butyl-benzyl)-(pyridine-3-sulfonyl)-amino]-methyl}-phenoxy)-acetic acid (1), an EP2 receptor-selective prostaglandin E2 agonist, is being developed to aid in the healing of bone fractures. To support the development of this program, in vitro metabolism of 1 was investigated in human liver microsomes and major recombinant human cytochrome P450 (P450) isoforms. 1 was meta...

Metabolism, pharmacokinetics, tissue distribution, and excretion of [14C]CP-424391 in rats.

CP-424391, 2-amino-N-[3aR-benzyl-2-methyl-3-oxo-2,3,3a,4,6,7-hexahydro-pyrazolo[4,3-c]pyridin-5-yl)-1R-benzyloxymethyl-2-oxoethyl]-isobutyramide, is an orally active growth hormone secretagogue currently being developed. In this study, we investigated the metabolic fate and disposition of radiolabeled CP-424391 in rats. Following 15 mg/kg single oral administration to Sprague-Dawley rats, 91% o...

Spinally mediated analgesic interaction between γ-aminobutyric acid B receptor agonist and glutamate receptor antagonists in rats

Background.  Many mechanisms are involved in pain transmission in the spinal cord.  Therefore, combination of drugs acting on different kinds of mechanisms might be useful for analgesia.  We investigated the interaction betweenγ-aminobutyric acid （GABA）B receptor agonist, baclofen, and N-methyl-D-aspartate （NMDA） receptor antagonist, AP-5, orα-amino-3-hydroxy-5-methylisoxazole-4-propionic acid ...

The selective activation of the glutamate receptor GluR5 by ATPA is controlled by serine 741.

Only a few agonists exhibit selectivity between the AMPA and the kainate subtypes of the glutamate receptor. The most commonly used kainate receptor preferring agonist, (S)-2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid [(S)-ATPA], is an (R,S)-2-amino-3-(5-methyl-3-hydroxy-4-isoxazolyl)propionic acid (AMPA) derivative in which the methyl group at the 5-position of the isoxazole r...