BDZs, Designer BDZs and Z-drugs: Pharmacology and Misuse Insights

Abstract

: Benzodiazepines (BZDs) are a widely prescribed class of sedative-hypnotics compounds for the treatment of a broad range of conditions as anxiety and obsessive-compulsive disorders, phobias, sleep related problems associated with insomnia and for the management of alcohol and GHB withdrawal. Zolpidem, zopiclone and zaleplon, commonly known as Z-drugs are non-benzodiazepine hypnotic drug with pharmacology similar to BDZs. Despite their usefulness, BDZs and Z-drugs present a potential for abuse and dependence. Moreover, the non-medical use of BDZs is a well-known phenomenon and represents an increasingly widespread public health problem since is associated with an elevated risk of serious health consequences or fatal overdose, especially among specific group of users. The spectrum of BDZs and Z-drugs misuse is extended by new synthetic BDZs, which may pose high risks to users, since the majority have never undergone clinical trials or tests and consequently their pharmacology and toxicology is largely unknown.

Drug prescriptions preceding opioid-related deaths–a register study in forensic autopsy patients

“…It is worth noting that the five most dispensed drugs in this population all have potential for misuse, especially in populations with a previous history of addiction [ 11 , 14 , 20 , 21 , 41 – 45 ]. The use of BZD, z-drugs and pregabalin has great misuse potential [ 26 ] and has been shown to increase opioid-related mortality [ 6 – 11 , 13 , 20 ] and at least one of these drugs was present in the blood at the time of death in a vast majority of cases and they were among the drugs most frequently dispensed by this population in our material. Previous research suggests that individuals with opioid addiction are prescribed BZD in excessive amounts [ 15 , 16 ] and it is possible that excessive prescription of these drugs occurs in our material as well.…”

“…In addition to opioids, other prescription drugs used in combination with opioids increase the risk of opioid-related death. In particular, the use of benzodiazepines (BZD), but also the use of z-drugs (zopiclone, zolpidem) and pregabalin, is widespread among opioid-addicted individuals, often involved in opioid deaths, and seems to be associated with increased mortality in combination with opioids both when prescribed and used illicitly [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. An American study on veterans who were prescribed opioids concluded that simultaneous BZD prescription increased the risk of overdose death in a dose-response manner.…”

Cod liver oil nano-structured lipid carriers (Cod-NLCs) as a promising platform for nose to brain delivery: Preparation, in vitro optimization, ex vivo cytotoxicity & in vivo biodistribution utilizing radioiodinated zopiclone

“…This led to the development of non-benzodiazepines or as known ‘ Z -drugs’ ( Bragg et al, 2019 ); that were introduced to the market in the 1990s ( Brandt and Leong, 2017 ). Z-drugs have fewer side effects owing to their short half-live, selective drug profiles, and fewer drug-drug interactions ( Zaami et al, 2021 ). Zopiclone (ZP) is a type A γ-aminobutyric acid (GABA) receptor agonist that increases GABA-neuronal block ( Louzada et al, 2021b ).…”

The Prevalence of Benzodiazepine Use among Italian Drivers in 15,988 Cases of Driving License Regranting from 2015 to 2023: Risks and Implications for Driving Fitness

“…Concurrently, an increase in the number of self-reported benzodiazepine use (from one subject in 2015 to 152 in 2022 and 92 in 2023), was registered. The widespread availability of benzodiazepines and their relatively low cost increases the potential for the non-medical use of these medications [50].…”