A transdermal patch for delivering N,N-dimethyltryptamine (DMT) at low, non-hallucinogenic doses was developed and tested in mice. The patch provided consistent, extended drug release, achieving plasma levels below 60 ng/mL. Compared to intravenous administration, the patch extended DMT's half-life by 20-fold and achieved 77% bioavailability. Female and male mice showed notable differences during IV dosing, but transdermal delivery produced steady levels. A head twitch assay indicated no hallucinogenic effects at these low plasma concentrations. The patch could offer a non-invasive, outpatient treatment option for conditions where high, bolus doses are unnecessary.
Monoclonal antibodies were developed that specifically recognize (2R,6R)-hydroxynorketamine, a metabolite of ketamine linked to rapid antidepressant effects. An immunogenic bioconjugate was designed by attaching a 6-aminohexanoic acid linker to the pharmacophore and coupling it to a carrier protein. Mice immunized with this conjugate produced equivalent antibody titers to a racemic comparator. Hybridoma screening yielded the monoclonal antibody 6F11-HC1-LC2, which showed strong binding to (2R,6R)-hydroxynorketamine but no response to the (2S,6S) enantiomer in competitive ELISA. Surface plasmon resonance revealed sub-nanomolar affinity (0.4 nM) for (2R,6R)-hydroxynorketamine-BSA conjugates and over 150-fold selectivity over ketamine-BSA conjugates. These antibodies can be used in future studies to investigate the roles of hydroxynorketamine enantiomers in ketamine's antidepressant effects.