This review article takes a closer look at a new class of psychoactive substances called designer benzodiazepines (DBZs) and the challenges of their detection. These are adinazolam, clonazolam, deschloroetizolam, diclazepam, etizolam, flualprazolam, flubromazepam, flubromazolam, phenazepam, and pyrazolam. They are central nervous system depressants and sedatives that can cause psychomotor impairment and increase the overdose risk when combined with other sedatives. DBZs undergo phase I and II metabolism similar to traditional benzodiazepines, but their specific metabolic pathways and the influence of genetic polymorphisms are yet to be clarified. Advances in liquid chromatography-tandem mass spectrometry (LC-MS/MS) have enhanced the method's sensitivity for DBZs and their metabolites in biological samples and coupled with improved blood sampling methods require less blood for drug monitoring. Further research should focus on elucidating their pharmacokinetic properties and metabolism in humans, especially in view of genetic polymorphisms and drug interactions that could inform clinical treatment choices. Even though we have witnessed important advances in DBZ detection and measurement, further refinements are needed to expand the scope of detectable DBZs and their metabolites. All this should help toxicological research to better identify and characterise the risks of chronic and polydrug abuse and facilitate clinical, forensic, and regulatory responses to this growing issue.
Svrha je ovoga preglednog članka dati bolji uvid u djelovanje nove skupine psihoaktivnih tvari zvanih dizajnerski benzodiazepini (DBZ) i u izazove njihova otkrivanja. Poimence, to su adinazolam, klonazolam, deskloroetizolam, diklazepam, etizolam, flualprazolam, flubromazepam, flubromazolam, fenazepam i pirazolam. Riječ je o depresivima i sedativima središnjega živčanog sustava koji mogu oslabiti psihomotornu funkciju te povećati rizik od predoziranja u kombinaciji s ostalim sedativima. DBZ-i prolaze fazu I. i II. biorazgradnje na način sličan onomu tradicionalnih benzodiazepina, no tek nam preostaje razjasniti njihove specifične metaboličke putove i kako na njih utječu genski polimorfizmi. Poboljšanja u tekućinskoj kromatografiji s tandemskom masenom spektrometrijom (engl. liquid chromatography-tandem mass spectrometry, krat. LC-MS/MS) povećala su osjetljivost metoda na DBZ-e i njihove metabolite u biološkim uzorcima, a poboljšanja u uzorkovanju krvi smanjila su količine potrebne za praćenje razina tvari. Ipak, potrebna su daljnja istraživanja koja će rasvijetliti njihova farmakokinetička svojstva i metabolizam u ljudi, napose u smislu utjecaja genskih polimorfizama i interakcija lijekova, što će pomoći pri odabiru kliničkog liječenja. Premda smo svjedoci važnih pomaka u otkrivanju i mjerenju DBZ-a, potrebna su daljnja poboljšanja kako bi se povećao opseg DBZ-a i njihovih metabolita koji se ovim metodama mogu otkriti. Sve to trebalo bi ne samo pridonijeti toksikološkim istraživanjima radi boljeg prepoznavanja rizika povezanih s kroničnom kombiniranom zloporabom droga nego i olakšati kliničke, forenzičke i regulatorne postupke kao odgovor na ovaj rastući problem.
Keywords: adinazolam; clonazolam; deschloroetizolam; deskloroetizolam; diclazepam; diklazepam; etizolam; fenazepam; flualprazolam; flubromazepam; flubromazolam; klonazolam; masena spektrometrija; mass spectrometry; metabolism; metabolizam; phenazepam, pyrazolam; pirazolam; toksikologija; toxicology.
© 2023 Dihua Wu et al., published by Sciendo.