RT Journal Article
SR Electronic
T1 STUDIES ON THE METABOLISM AND PHARMACOLOGY OFα -[(2-PYRIDYLAMINO)METHYL]BENZYL ALCOHOL HYDROCHLORIDE (PHENYRAMIDOL HYDROCHLORIDE) IN RODENTS
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 140
OP 147
VO 2
IS 2
A1 NICHOLAS GERBER
A1 RICHARD A. SEIBERT
A1 DOMINIC M. DESIDERIO
A1 RICHARD M. THOMPSON
YR 1974
UL http://dmd.aspetjournals.org/content/2/2/140.abstract
AB 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 (t½) of P in control mice was about 15 min. Stimulation of the drug-metabolizing enzymes shortened the whole body t½ of P from 15 min to about 8 min, whereas treatment with SKF 525-A prolonged the t½ 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. Copyright © 1974 by The American Society for Pharmacology and Experimental Therapeutics