Drug development is lengthy, complex, and costly. In 2004, the FDA's 'Critical Path' document highlighted a gap between scientific advances and the drug development process, addressing microdosing. Microdosing uses extremely low, nonpharmacologically active doses to determine a drug's pharmacokinetic profile in humans. It offers a new tool that could complement traditional animal-to-human scaling and reshape phase I clinical research. As Phase 0 methods and technology advance, human microdosing may become applicable to more drugs in development.
Phencyclidine (PCP), a drug that induces psychotic symptoms resembling schizophrenia, blocks NMDA glutamate receptors in the brain. This experiment tested whether surgically removing the olfactory bulbs in rats altered the effects of a single high dose of PCP (10 mg/kg) on behavior. PCP increased home-cage movement in both bulbectomized and sham-operated animals over three hours, with slightly greater activity in the sham group. PCP also suppressed grooming, rearing, and side-falling while increasing circling and head rolling in both groups, though these behavioral changes were not statistically significant. The results suggest that olfactory bulb removal does not alter NMDA receptor activity.