| First Author | Rais R | Year | 2012 |
| Journal | Drug Metab Dispos | Volume | 40 |
| Issue | 11 | Pages | 2067-73 |
| PubMed ID | 22837388 | Mgi Jnum | J:228710 |
| Mgi Id | MGI:5708528 | Doi | 10.1124/dmd.112.046482 |
| Citation | Rais R, et al. (2012) Pharmacokinetics of oral D-serine in D-amino acid oxidase knockout mice. Drug Metab Dispos 40(11):2067-73 |
| abstractText | D-Amino acid oxidase (DAAO) catalyzes the oxidative deamination of D-amino acids including D-serine, a full agonist at the glycine modulatory site of the N-methyl-d-aspartate (NMDA) receptor. To evaluate the significance of DAAO-mediated metabolism in the pharmacokinetics of oral D-serine, plasma D-serine levels were measured in both wild-type mice and transgenic mice lacking DAAO. Although D-serine levels were rapidly diminished in wild-type mice (t((1/2)) = 1.2 h), sustained drug levels over the course of 4 h (t((1/2)) > 10 h) were observed in mice lacking DAAO. Coadministration of D-serine with 6-chlorobenzo[d]isoxazol-3-ol (CBIO), a small-molecule DAAO inhibitor, in wild-type mice resulted in the enhancement of plasma D-serine levels, although CBIO seems to have only temporary effects on the plasma D-serine levels due to glucuronidation of the key hydroxyl group. These findings highlight the predominant role of DAAO in the clearance of D-serine from the systemic circulation. Thus, a potent DAAO inhibitor with a longer half-life should be capable of maintaining high plasma D-serine levels over a sustained period of time and might have therapeutic implications for the treatment of schizophrenia. |
