| PD 0158771 is a novel antipsychotic discontinued in the early stages of development at Parke-Davis Pharmaceutical Research. The compound, a dopamine (DA) D2, D3, and serotonin 5-HT1A receptor agonist, was investigated for treatment of schizophrenia. Objectives of this research were to investigate tissue distribution, excretion, metabolic profile, and major metabolites in intact rats following a single oral or intravenous dose of [14C] PD 0158771, as this information may aid in the development of similar compounds.; These studies showed that the compound was rapidly excreted (90% of dose) within the first 24 hours postdose. Urinary metabolites were determined by HPLC profiling with in-line radioactivity detection and identified as monohydroxy-PD 0158771, di-hydroxy-PD 0158771, a glucuronide conjugate of di-hydroxy-PD 0158771, and a di-glucuronide conjugate of di-hydroxy-PD 0158771 using tandem LC-MS/MS. Distribution experiments using Whole Body Autoradiographic techniques showed radioequivalents of PD 0158771 crossed the blood-brain barrier regardless of dose route, indicating that the drug or a metabolite reaches the intended target. Results described here offer insight into the metabolic disposition of PD 0158771. |
