Metabolites of methohexitone do not contribute to its prolonged action on the central nervous system.
Methohexitone has been reported to have a prolonged action on the central nervous system (CNS) despite its relatively short elimination half-life. A hydroxy metabolite of methohexitone was identified, purified and isolated from the urine collected from eight surgical patients and five mongrel dogs anaesthetized with methohexitone. Using a rotarod device, the CNS-activity of the human and canine metabolites was tested in mice and compared to that of methohexitone. In this test, the metabolites showed CNS-depressant activity, but the ED50 (dose needed to affect 50% of the animals) of the metabolites was ten times higher than the ED50 of the parent drug. Because in patients, no traces of the hydroxy metabolite could be found in blood, and in dogs the plasma concentration of the metabolite was about two-thirds of that of the parent compound, it is unlikely that the residual CNS-effects of methohexitone are due to its major metabolite, hydroxymethohexitone.
Korttila
K
K
Department of Anesthesia and Critical Care, University of Chicago.
Ghoneim
M M
MM
Chiang
C K
CK
Nuotto
E
E
Fischer
L J
LJ
D000818:Animals; D001921:Brain / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002849:Chromatography, Gas; D004285:Dogs; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D008723:Methohexital / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology / Q000652:urine; D051379:Mice; D004856:Postural Balance / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects*; D013997:Time Factors
C033408:4'-hydroxymethohexital; D008723:Methohexital