STUDIES ON THE METABOLISM AND PHARMACOLOGY OF -[(2-PYRIDYLAMINO)METHYL]BENZYL ALCOHOL HYDROCHLORIDE (PHENYRAMIDOL HYDROCHLORIDE) IN RODENTS

¹ Department of Pharmacology, University of Oregon Medical School
² Department of Pharmacology, Baylor College of Medicine
³ Department of Biochemistry and Institute for Lipid Research, Baylor College of Medicine
⁴ Institute for Lipid Research, Baylor College of Medicine

A specific ultraviolet assay for phenyramidol (P) has been developed. In rodents the drug produces a reversible loss of the righting reflex. Control mice which received 8 mg ip of P hydrochloride remained paralyzed for 35.6 ± 2.5 (SE) min, whereas animals whose drug-metabolizing enzymes had been stimulated by pretreatment with diphenylhydantoin were paralyzed for 7.3 ± 2.8 min. Pretreatment with SKF 525-A (40 mg/kg ip) significantly prolonged P paralysis time from 6.3 ± 1.8 min to 24.9 ± 3.5 min in mice that received 5 mg of P hydrochloride ip. The biological half-life (t) of P in control mice was about 15 min. Stimulation of the drug-metabolizing enzymes shortened the whole body t of P from 15 min to about 8 min, whereas treatment with SKF 525-A prolonged the t to 38 min. Stimulation of the liver microsomal enzymes by pretreatment of mice also doubled the rate of metabolism of P in incubations of P with liver microsomes. P is rapidly metabolized in the isolated perfused rat liver. Metabolites which have been identified by gas chromatography and mass spectrometry include P glucuronide, a product formed by hydroxylation of the pyridine ring and the glucuronide of the latter. Gas chromatography indicated that P glucuronide accounted for at least 90% of the total metabolite.