Benzodiazepines and Designer Drugs

Benzodiazepine derivatives – anxiolytics that relieve anxiety, in the old way are called tranquilizers. Drugs in this group enhance the effects of GABA (gamma-amino-butyric acid), the main inhibitory mediator in the central nervous system. Weakly act on serotonin and dopamine receptors. The effects are due to the influence on various parts of the central nervous system: the reticular formation of the brain stem and nonspecific nuclei of the thalamus (sedation), amygdala complexes of the limbic system (anxiolytic), polysynapses of the spinal cord (muscle relaxant) and hippocampus (anticonvulsant). Sedation caused by benzodiazepines is manifested by suppression of the reaction to persistent stimuli with a decrease in the level of thinking and activity. They are characterized by anterograde amnesia, when it is impossible to remember what happened during the action of the drug. At the same time, contact with the patient is maintained. This complication, by the way, can be very convenient for unpleasant medical procedures, including chemotherapy. The drugs of this group are anesthetics and, in combination with other drugs, can be used in palliative oncology as pain relievers.

The presence of very beneficial properties has caused overuse of these drugs, which leads to psychological and physical dependence. In the early 1990s, benzodiazepines were the 18th-20th most consumed drugs in the United States.

Diazepam (sibazone, seduxen, relanium) can be useful for stopping delayed vomiting, since it has an injectable form. Diazepam is more lipophilic than lorazepam, so the effects of the latter on the central nervous system are delayed. The rate of metabolic transformation and elimination is too low, so the main effects are long lasting. The half-life of lorazepam is from 10 to 18 hours, diazepam is 48-150 hours, and phenozepam is up to 18 hours.

Long half-lives can lead to undesirable excessive depression of the central nervous system and are due to the formation of active forms of metabolites. The half-life of diazepam increases with age, but its elimination from the body remains constant. On the other hand, the shorter the elimination half-life, the more severe the “withdrawal” syndrome inherent in tranquilizers, since the trace concentrations of the drug remain in the plasma for a long time. Withdrawal is strongly reminiscent of an alcoholic hangover. For drugs in this group, pronounced cross-dependence is characteristic, when withdrawal symptoms caused, for example, by lorazepam, can be stopped by taking diazepam or fenozepam, and vice versa. Classical physical dependence, however, develops very rarely, only with long-term administration of very high doses, for diazepam it is 8-10 tablets per day for more than 2-3 months. For most sleeping pills (except benzodiazepines), a dose 10 times the sleeping pill can be lethal. There is an antidote for benzodiazepines – flumazenil. But the main disadvantage of benzodiazepines is the increased depression of the central nervous system when taken together with other sedative-hypnotics or alcohol.

List of Benzodiazepines and Designer Drugs:
Drug name Common trade names Year approved (US FDA) Approx. equivalent oral doses to 10 mg diazepam (mg) Time to peak onset of action(hours) Elimination half-life of active metabolite (hours) Therapeutic use
Adinazolam Deracyn Research chemical   1–2 3 anxiolytic, antidepressant
Alprazolam Xanax, Helex, Xanor, Trankimazin, Onax, Alprox, Misar, Restyl, Solanax, Tafil, Neurol, Frontin, Kalma, Ksalol 1981 0.25 1–2 10–20 anxiolytic, antidepressant
Bentazepam Thiadipona     1–3 2–4 anxiolytic
Bretazenil         2.5 anxiolytic, anticonvulsant
Bromazepam Lectopam, Lexaurin, Lexatin, Lexotanil, Lexotan, Bromam 1981 6 1–3 20–40 anxiolytic,hypnotic
Bromazolam   Research chemical       anxiolytic
Brotizolam Lendormin, Dormex, Sintonal, Noctilan     0.5–2 4–5 hypnotic
Camazepam Albego, Limpidon, Paxor     0.5–2 6–29 anxiolytic
Chlordiazepoxide Librium, Risolid, Elenium 1960 25 1.5–4 5–200 anxiolytic
Cinazepam Levana     2–4 60 hypnotic, anxiolytic
Cinolazepam Gerodorm     0.5–2 9 hypnotic
Clobazam Onfi, Frisium, Urbanol 2011   1–3 8–60 anxiolytic, anticonvulsant
Clonazepam Rivatril, Rivotril, Klonopin, Iktorivil, Paxam 1975 0.5 1–4 19.5–50 anticonvulsant, anxiolytic, muscle relaxant
Clonazolam   Research chemical 0.2 0.5–1.5 10–18 anxiolytic, anticonvulsant, hypnotic, muscle relaxant
Clorazepate Tranxene, Tranxilium 1972 20 Variable 32–152 anxiolytic, anticonvulsant
Clotiazepam Veratran, Clozan, Rize     1–3 4 anxiolytic
Cloxazolam Sepazon, Olcadil     2–5 80–105 anxiolytic, anticonvulsant
Delorazepam Dadumir     1–2 80–105 anxiolytic, amnesic
Deschloroetizolam   Research chemical       anxiolytic
Diazepam Antenex, Apaurin, Apzepam, Apozepam, Diazepan, Hexalid, Normabel, Pax, Stesolid, Stedon, Tranquirit, Valium, Vival, Valaxona 1963 10 1–1.5 32–205 anxiolytic, anticonvulsant, muscle relaxant, amnesic
Diclazepam   Research chemical   1.5–3 42 anxiolytic, amnesic, anticonvulsant, hypnotic, muscle relaxant
Estazolam ProSom, Nuctalon 1990   1–5 10–31 hypnotic, anxiolytic
Ethyl carfluzepate   Not approved   1–5 11–24 hypnotic
Etizolam Etilaam, Etizest, Pasaden, Depas Often sold as a research chemical, but is approved for human use in many countries. Controlled substance in some US states, Canada, Germany, Austria, and others. 1–2 1–2 6 anxiolytic, hypnotic, amnesic, muscle relaxant, anticonvulsant
Ethyl loflazepate Victan, Meilax, Ronlax   2 2.5–3 73–119 anxiolytic
Flualprazolam   Research chemical       hypnotic, anxiolytic
Flubromazepam   Research chemical   1.5–8 100–220 anxiolytic, hypnotic, amnesic, muscle relaxant, anticonvulsant
Flubromazolam   Research chemical       hypnotic
Fluclotizolam   Research chemical       hypnotic
Flunitrazepam Rohypnol, Hipnosedon, Vulbegal, Fluscand, Flunipam, Ronal, Rohydorm, Hypnodorm Not approved 1 0.5–3 18–200 hypnotic
Flunitrazolam   Research chemical       hypnotic
Flurazepam Dalmadorm, Dalmane, Fluzepam 1970 15 1–1.5 40–250 hypnotic
Flutazolam Coreminal       3.5 hypnotic
Flutoprazepam Restas Research chemical   0.5–9 60–90 hypnotic, anticonvulsant
Halazepam Paxipam 1981 20 1–3 30–100 anxiolytic
Ketazolam Anxon Not approved 20 2.5–3 30–200 anxiolytic
Loprazolam Dormonoct   1.5 0.5–4 3–15 hypnotic
Lorazepam Ativan, Orfidal, Lorenin, Lorsilan, Temesta, Tavor, Lorabenz 1977 1 2–4 10–20 anxiolytic, amnesic, anticonvulsant, hypnotic, muscle relaxant
Lormetazepam Loramet, Noctamid, Pronoctan   1 0.5–2 10 hypnotic
Meclonazepam   Research chemical       anxiolytic
Medazepam Nobrium, Ansilan, Mezapam, Rudotel, Raporan   10 1–1.5 36–200 anxiolytic
Metizolam   Research chemical 2–4   12 anxiolytic, hypnotic, amnesic, muscle relaxant, anticonvulsant
Mexazolam Melex, Sedoxil     1–2   anxiolytic
Midazolam Dormicum, Versed, Hypnovel, Dormonid 1985 10 (oral)4 (IV) 0.5–1 1.5–2.5 hypnotic, anticonvulsant, amnesic
Nifoxipam   Research chemical       hypnotic
Nimetazepam Erimin     0.5–3 14–30 hypnotic
Nitemazepam   Research chemical        
Nitrazepam Mogadon, Alodorm, Pacisyn, Dumolid, Nitrazadon 1965 10 0.5–3 17–48 hypnotic, anticonvulsant
Nitrazolam   Research chemical       hypnotic
Nordiazepam Madar, Stilny       30–150 anxiolytic
Norflurazepam   Research chemical       hypnotic
Oxazepam Seresta, Serax, Serenid, Serepax, Sobril, Oxabenz, Oxapax, Oxascand, Ox-Pam, Opamox, Alepam, Medopam, Murelax, Noripam, Purata 1965 25 3–4 4–11 anxiolytic
Phenazepam Phenazepam, Phenzitat Research chemical   1.5–4 60 anxiolytic, anticonvulsant
Pinazepam Domar       40–100 anxiolytic
Prazepam Lysanxia, Centrax Not approved 15 2–6 36–200 anxiolytic
Premazepam   Not approved   2–6 10–13 anxiolytic
Pyrazolam   Research chemical   1–1.5 16–18[23] anxiolytic, amnesic
Quazepam Doral 1985 20 1–5 39–120 hypnotic
Rilmazafone Rhythmy       11 hypnotic
Temazepam Restoril, Normison, Euhypnos, Temaze, Tenox 1981 20 0.5–3 4–11 hypnotic, anxiolytic, muscle relaxant
Tetrazepam Myolastan     1–3 3–26 muscle relaxant
Triazolam Halcion, Rilamir 1982 0.25 0.5–2 2 hypnotic
Drug name Common trade names Year approved Approx. equivalent oral doses to 10 mg diazepam (mg) Time to peak onset of action (hours) Elimination half-life of active metabolite (hours) Therapeutic use

Atypical benzodiazepine receptor ligands

Drug name Common trade names Year approved (US FDA) Elimination half-lifeof active metabolite (hours) Therapeutic use
DMCM       anxiogenic, convulsant
Flumazenil Anexate, Lanexat, Mazicon, Romazicon   1 antidote
Eszopiclone§ Lunesta 2004 6 hypnotic
Zaleplon§ Sonata, Starnoc 1999 1 hypnotic
Zolpidem§ Ambien, Nytamel, Sanval, Stilnoct, Stilnox, Sublinox (Canada), Xolnox, Zoldem, Zolnod 1992 2.6 hypnotic
Zopiclone§ Imovane, Rhovane, Ximovan; Zileze; Zimoclone; Zimovane; Zopitan; Zorclone, Zopiklone   4–6 hypnotic


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