Intrahepatic circulation of14C-phenazepam and its metabolites in albino rats

Bogatskii, A. V.; Golovenko, N. Ya.; Zin’kovskii, V. G.

doi:10.1007/bf00835494

Cited by 5 publications

(5 citation statements)

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“…At high doses, delirium and psychosis-like behaviour have been reported [ 46 ]. Phenazepam and its active metabolite are both GABA A receptor positive allosteric modulators [ 47 , 48 ]. In Russia and in other countries in which is legally marketed, phenazepam is available as 0.5-1 mg tablets, injectable solutions (0.1%, 0,3%) and transdermal patches, with a usual therapeutic oral dosage of 0.5 mg 2-3 times per day, and a maximum tolerated dose of 10 mg daily [ 33 , 49 , 50 ].…”

Section: Resultsmentioning

confidence: 99%

‘New/Designer Benzodiazepines’: An Analysis of the Literature and Psychonauts’ Trip Reports

Orsolini

Corkery

Chiappini

et al. 2020

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Background: NPS belonging to the benzodiazepine (BZD) class, e.g., ‘legal/designer BZDs’/‘research chemicals’, have recently emerged on the drug (mainly online/virtual) market. Objective: Whilst certain NPS belonging to the BZD class possess pharmacological profiles similar to controlled pharmaceutical BZDs, clinical and pharmacological profiles of current emerging BZDs are still not well-described. Therefore, there is a need to increase clinicians’/public health knowledge/awareness, to incentive harm reduction strategies. Method: A comprehensive overview was carried out by using the EMCDDA/EDND database regularly monitored by our research team, by specifically looking at the ‘new BZDs’ so far notified. Furthermore, given the limitation of peer-reviewed data published so far, a nonparticipant multilingual qualitative netnographic study was conducted to obtain further clinical/pharmacological/toxicological data, including psychonauts’ online trip reports. Results: First designer BZDs appeared as NPS around 2007. So far, 29 designer BZDs have been notified to the EMCDDA, being some of them extremely powerful, also at lower dosages. They are sold as tablets/powder/pellets/capsules/blotters/liquids, at very affordable prices, and variably administered. Some are also sold on the illicit drugmarket as counterfeit forms of traditional BZDs or as either adulterants or diluents in heroin or other synthetic opioids/cannabinoids. Nowadays, there is no guarantee of the quality of designer BZDs composition/purification and, hence, most NPS consumers may be inadvertently exposed to unsafe and harmful compounds. Conclusions: Given the limited information on their pharmacology/toxicity, variations in dosage, onset of effects, combination of substances, potency, and general patient or individual variability, the concomitant use of these substances with other drugs entails several and unpredictable risks.

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Section: Resultsmentioning

confidence: 99%

‘New/Designer Benzodiazepines’: An Analysis of the Literature and Psychonauts’ Trip Reports

Orsolini

Corkery

Chiappini

et al. 2020

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“…[24] In a human study in which subjects were given 7 mg of phenazepam the metabolites 3-hydroxyphenazepam, ABPH and another unnamed metabolite, (Figure 1) were detected in urine in living subjects [29] and in a more recent study of phenazepam abuse in Finland 3-hydroxyphenazepam was detected in blood and urine again in living subjects. [8] Another metabolite (6-bromo-(2chlorophenyl) quinazoline-2-one (QNZ) has been suggested based on animal studies [30] but as yet has not been observed in human studies. The quantitation of 3-hydroxyphenazepam appears problematic as to date no validated methods have appeared in the western literature and the only previous paper mentioned that 3-hydroxyphenazepam may be thermally unstable undergoing thermal dehydration.…”

Section: Resultsmentioning

confidence: 99%

Analysis of phenazepam and 3‐hydroxyphenazepam in post‐mortem fluids and tissues

Crichton

Shenton

Drummond

et al. 2015

Drug Testing and Analysis

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Phenazepam is a benzodiazepine that is predominantly used clinically in the former Soviet states but throughout the wider world is being abused. This study reports the tissue distribution and concentration of both phenazepam and 3-hydroxyphenazepam in 29 cases quantitated by LC-MS/MS in a variety of postmortem fluids (subclavian blood, femoral blood, cardiac blood, urine, vitreous humor) and tissues (thalamus, liver and psoas muscle). In 27 cases the cause of death was not directly related to phenazepam (preserved (fluoride/oxalate) femoral blood phenazepam concentrations 0.007 mg/L to 0.360 mg/L (median 0.097 mg/L)). In two cases phenazepam was either a contributing factor to, or the certified cause of death (preserved (fluoride/oxalate) femoral blood 0.97 mg/L and 1.64 mg/L). The analysis of phenazepam and 3-hydroxyphenazepam in this study suggests that they are unlikely to be subject to large postmortem redistribution and that there is no direct correlation between tissues/fluid and femoral blood concentrations. Preliminary investigations of phenazepam stability comparing femoral blood phenazepam concentrations in paired preserved (2.5% fluoride/oxalate) and unpreserved blood show that unpreserved samples show on average a 14% lower concentration of phenazepam and we recommend that phenazepam quantitation is carried out using preserved samples wherever possible.

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“…Pharmacologically both phenazepam and 3-hydroxy-phenazepam have been described as full g-aminobutyric acid type A (GABA A ) receptor agonists 17,21 and both appear to be pharmacologically active with greater potency than diazepam probably due to the bromine atom in the molecule. The two other metabolites of phenazepam, QNZ and ABPH, also appear to have pharmacological activity, at least in in vitro experiments.…”

Section: Pharmacodynamicsmentioning

confidence: 99%

“…QNZ and ABPH exhibited biphasic effects at the GABA A receptor initially potentiating GABA responses at low concentrations and then inhibiting them at higher micromolar concentrations; however, these metabolites are only likely to have significant in vivo pharmacological effects in overdose situations. 17,21 ABPH is also thought to act at both glycine and Nmethyl-D-aspartate (NMDA) receptors again at high micromolar concentrations. 22 …”

Section: Pharmacodynamicsmentioning

confidence: 99%

“…There may also be glucuronides of some of the metabolites, as these have been found in rat studies. 17 Limited information is available about the prevalence of the various metabolites in humans. A study in which a 5-mg oral dose of phenazepam was given to healthy volunteers resulted in 3-hydroxy-phenazepam being detected in the urine but not in blood samples.…”

Section: Metabolismmentioning

confidence: 99%

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