Diazepam and N-desmethyldiazepam are found in rat brain and adrenal and may be of plant origin

Wildmann, Johannes; Möhler, Hanns; Vetter, W

doi:10.1016/0378-8741(88)90053-0

Cited by 3 publications

(3 citation statements)

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“…Positive detection of diazepam in various biological samples is often of problematic interpretation because alternative explanations exist other than drug use. First, it has been shown in the past that the serum of unmedicated humans may contain diazepam together with its main active metabolites at concentrations of 1-32 ng/L, possibly as the result of benzodiazepines naturally being present in certain foods [17][18][19]. Secondly, the presence of diazepam without metabolites does not provide unequivocal evidence of diazepam exposure.…”

Section: Woman #2mentioning

confidence: 98%

Hair analysis of drugs involved in drug-facilitated sexual assault and detection of zolpidem in a suspected case

Salomone¹,

Gerace²,

Corcia³

et al. 2011

Int J Legal Med

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In drug-facilitated crimes, victims are subjected to nonconsensual acts while they are incapacitated by the effects of a drug. A specific LC-MS/MS protocol for determining benzodiazepines and hypnotics at low concentration in hair specimens was developed and validated in order to target the allegedly administered drugs on a chronological basis. In the case hereby reported, a 26-year-old woman claimed to have been sexually assaulted after being administered an allegedly drugged coffee, but toxicological analysis of urine and blood provided no evidence of any drug intake. Subsequently, a second woman accused the same man of sexual abuse. Hence, the suspect was prosecuted. Specimens were collected from four subjects (two alleged victims, the suspect and his wife) and segmental hair analysis was performed. The results revealed that zolpidem was present at low picogram per milligram concentration in three out of eleven segments of hair specimen obtained from the first of the alleged victims, offering plain evidence of single or sporadic exposure, whereas the agent was detected in the high picogram per milligram range in the hair collected from suspect's wife, coherently with therapeutic administration. The presence of interfering signals typical of the keratin-containing matrix was found and possible hair degradation by cosmetic treatments was investigated by electron microscopy, so as to obtain a judicious interpretation of the analytical findings.

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Section: Woman #2mentioning

confidence: 98%

Hair analysis of drugs involved in drug-facilitated sexual assault and detection of zolpidem in a suspected case

Salomone¹,

Gerace²,

Corcia³

et al. 2011

Int J Legal Med

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“…1) is the most prominent representative of the 1,4-benzodiazepines (BZs), a group of synthetical anxiolytics and sedatives, the first representatives of which were initially synthesized by Sternbach in the late fifties (see Schlitz, 1982;Archer and Sternbach, 1968). Completely unexpectedly, since 1986, several benzodiazepines, among them also authentic 1, were identified in mammalian brain and other organs (see Sangameswaran and De Blas, 1985;Klotz, 1989;Wildmann et al, 1987). In the course of the investigation of their origin, these compounds were then likewise found in several foodstuffs, among them potatoes and cereals (see Wildmann et al, 1988;Unseld and Klotz, 1989;Graf, 1990).…”

Section: Introductionmentioning

confidence: 97%

A first biosynthetic proposal for the in vivo formation of naturally occurring diazepam-like 1,4-benzodiazepines

Bringmann¹

1992

J. Neural Transmission

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A first rational concept for the in vivo formation of naturally occurring diazepam-type 1,4-benzodiazepines is suggested--by oxidative carbon-carbon bond cleavage of the known quinoline alkaloid viridicatin, a fungal metabolite from Penicillium species, replacement of the resulting N-oxaloyl substituent by a glycinoyl residue, and subsequent ring closure under Schiff base formation. In principle, all the proposed individual reaction steps as such are known from the literature: they have either been proven to occur in vivo, or they have been performed chemically. According to this concept, diazepam-type benzodiazepines would not only represent the joint result of both industrial developments and evolutionary processes in nature, but would even arise from identical precursors--ortho-aminobenzophenone and glycine! Alternatively, according to a slightly modified (more "economical") biogenetic concept, the oxaloyl residue would not be substituted, but rather converted into the glycinoyl part. This hypothetic biosynthesis of naturally occurring 1,4-benzodiazepines might proceed in part in microorganisms (e.g. in fungi) and in part in higher organisms (e.g. in plants).

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“…In the course of the search for natural ligands of the benzodiazepine receptor, completely unexpectedly authentic diazepam (Valium | 1), nordiazepam (2), and also nonhalogenated analogs like deschlorodiazepam (3), were found to occur, in trace amounts, in human (see Klotz, 1990), mammalian (see Wildmann et al, 1987;Medina et al, 1988;Unseld et al, 1989) and plant tissues (see Wildmann, 1988;Unseld et al, 1989). A contamination of the samples by BZs from industrial sources was ruled out after BZs like 3 without therapeutical use were detected (see Wildmann et al, 1987). Furthermore, BZ activity was found in human brains that had been stored in paraffin since 1940 -about twenty years before the first BZ synthesis in a chemist's laboratory (see Sangameswaran, 1986)!…”

Section: Introductionmentioning

confidence: 98%

In vivo formation of diazepam-like 1,4-benzodiazepines byPenicillium verrucosum var.verrucosum after administration of 2-aminobenzophenones and glycine

Bringmann

Mäder

1995

J. Neural Transmission

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The in vivo formation of the diazepam-like 1,4-benzodiazepine deschloronordiazepam from its assumed biogenetic precursors, 2-amino-benzophenone and glycine, by the mould strain Penicillium verrucosum var. verrucosum, is described. Deschloronordiazepam formation was established by GC/MSD analysis monitoring characteristic fragment patterns of the benzodiazepine moiety. The identification of deschloronordiazepam was confirmed by feeding experiments of D5-2-aminobenzophenone, as well as its brominated and chlorinated derivatives to the mould. The formation of the 1,4-benzodiazepine was observed to depend on various factors, e.g. the time of application of the precursors, duration of the incubation and kind of cultivation. The results represent the first actual de novo synthesis of such diazepam-like 1,4-benzodiazepines from plausible biosynthetic precursors in a living organism, in agreement with a biosynthetic concept recently established in our group. Such pharmacologically active 1,4-benzodiazepines had been detected in trace amounts in mammalian and plant tissues. Because of their unusual molecular framework, they had previously been considered not to fit into any conventional biosynthetic route.

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Diazepam and N-desmethyldiazepam are found in rat brain and adrenal and may be of plant origin

Cited by 3 publications

References 0 publications

Hair analysis of drugs involved in drug-facilitated sexual assault and detection of zolpidem in a suspected case

Hair analysis of drugs involved in drug-facilitated sexual assault and detection of zolpidem in a suspected case

A first biosynthetic proposal for the in vivo formation of naturally occurring diazepam-like 1,4-benzodiazepines

In vivo formation of diazepam-like 1,4-benzodiazepines byPenicillium verrucosum var.verrucosum after administration of 2-aminobenzophenones and glycine

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