Distribution of venlafaxine in three postmortem cases.
Venlafaxine (V) is a second-generation antidepressant approved for use in the United States in 1993. It is a derivative of phenethylamine and is structurally unrelated to first- and other second-generation antidepressants. Nevertheless, its mechanism of action is similar to other antidepressants; it inhibits the reuptake of presynaptic norepinephrine and serotonin. Its major routes of elimination involve O and N demethylation. O-Desmethylvenlafaxine (ODV) is biologically active. Therapeutic concentrations of V and ODV are approximately 0.2 and 0.4 mg/L, respectively. Three cases of drug intoxication involving V are presented. V and ODV were identified by gas chromatography-nitrogen-phosphorus detection after alkaline extraction of the biological specimen. On an HP-5 column, V and ODV elute after bupropion and fluoxetine, but prior to the first-generation antidepressants, sertraline, amoxapine, and trazodone. V and ODV were confirmed by full scan electron impact gas chromatography-mass spectrometry. The heart-blood V and ODV concentrations (mg/L) in the three cases were 6.6 and 31; 84 and 15; and 44 and 50, respectively. In Case 1, acetaminophen and diphenhydramine were found in the heart blood at 140 and 2.6 mg/L respectively. In Case 2, amitriptyline, nortriptyline, and chlordiazepoxide were found in the blood at 2.8, 0.5 and 3.3 mg/L, respectively. In each case, the manner of death was suicide.
Levine
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B
Office of the Chief Medical Examiner, State of Maryland, Baltimore 21201, USA.
Jenkins
A J
AJ
Queen
M
M
Jufer
R
R
Smialek
J E
JE
D000082:Acetaminophen / Q000097:blood / Q000378:metabolism / Q000652:urine; D000328:Adult; D000639:Amitriptyline / Q000097:blood / Q000378:metabolism / Q000652:urine; D018687:Antidepressive Agents, Second-Generation / Q000097:blood* / Q000378:metabolism / Q000652:urine; D001646:Bile / Q000378:metabolism; D002707:Chlordiazepoxide / Q000097:blood / Q000378:metabolism / Q000652:urine; D002849:Chromatography, Gas; D003511:Cyclohexanols / Q000097:blood* / Q000378:metabolism / Q000652:urine; D004155:Diphenhydramine / Q000097:blood / Q000378:metabolism / Q000652:urine; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008745:Methylation; D008875:Middle Aged; D009661:Nortriptyline / Q000097:blood; D012015:Reference Standards; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood*; D013405:Suicide; D000069470:Venlafaxine Hydrochloride
D000082:Acetaminophen; D000639:Amitriptyline; D018687:Antidepressive Agents, Second-Generation; D002707:Chlordiazepoxide; D003511:Cyclohexanols; D004155:Diphenhydramine; D009661:Nortriptyline; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride