Sex-dependent metabolism of ketamine and (2R,6R)-hydroxynorketamine in mice and humans.

ABSTRACT:

Background

Ketamine is rapidly metabolized to norketamine and hydroxynorketamine (HNK) metabolites. In female mice, when compared to males, higher levels of (2R,6R;2S,6S)-HNK have been observed following ketamine treatment, and higher levels of (2R,6R)-HNK following the direct administration of (2R,6R)-HNK.

Aim

The objective of this study was to evaluate the impact of sex in humans and mice, and gonadal hormones in mice on the metabolism of ketamine to form norketamine and HNKs and in the metabolism/elimination of (2R,6R)-HNK.

Methods

In CD-1 mice, we utilized gonadectomy to evaluate the role of circulating gonadal hormones in mediating sex-dependent differences in ketamine and (2R,6R)-HNK metabolism. In humans (34 with treatment-res

SUBMITTER: Highland JN 

PROVIDER: S-EPMC9904319 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature