Clinical data | |
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Dependence liability | Very high |
Routes of administration | Oral |
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Chemical and physical data | |
Formula | C17H12ClN5O2 |
Molar mass | 353.77 g·mol−1 |
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Clonazolam (also known as clonitrazolam) is a drug of the triazolobenzodiazepine (TBZD) class, which are benzodiazepines (BZDs) fused with a triazole ring. Although little research has been done about its effects and metabolism, it is sold online as a designer drug. [2] [3] [4] [5] [6]
The synthesis of clonazolam was first reported in 1971 and the drug was described as the most active compound in the series tested. [7]
Depending on dose consumed, clonazolam may pose comparatively higher risk than other designer benzodiazepines due to its ability to produce strong sedation and amnesia at doses as small as 0.5 mg. [2] [8]
In the UK, clonazolam has been classified as a Class C drug by the May 2017 amendment to The Misuse of Drugs Act 1971 along with several other designer benzodiazepine drugs. [9]
It is a Schedule I controlled substance in the United States and is not FDA approved for human consumption. Virginia state law has declared all of the following related medications are Schedule I: clonazolam, etizolam, flualprazolam, flubromazolam, and flubromazepam. [10] Minnesota declared clonazolam a Schedule I drug in August 2020.[ citation needed ]
On December 23, 2022, the DEA announced it had begun consideration on the matter of placing clonazolam under temporary Schedule I status. [11] Later on July 25, 2023, the DEA published a pre-print notice that clonazolam would become temporarily scheduled as a controlled substance from 26 July 2023 to 26 July 2025. [12]
In Australia, clonazolam is Schedule 9 under federal law. [13]
Sweden's public health agency suggested classifying clonazolam as a hazardous substance on June 1, 2015. [14]
Clonazolam's effects are similar to other benzodiazepines, such as anxiolysis, disinhibition, lethargy, muscle relaxation, and euphoria. [2] [8] While no dose of clonazolam is considered "safe" due to its lack of research and extreme potency, doses higher than 0.5 mg can cause benzodiazepine overdose in some individuals. [2] [8] The effects of a benzodiazepine overdose include sedation, confusion, amnesia, insufficient breathing, loss of consciousness, and death. [2] [8] Because dependence can occur in a short period of time, or even with a large initial dose, withdrawal symptoms (including seizures and death) may occur acutely following the period of intoxication. [2] [8]
Flunitrazepam, sold under the brand name Rohypnol among others, is a benzodiazepine used to treat severe insomnia and assist with anesthesia. As with other hypnotics, flunitrazepam has been advised to be prescribed only for short-term use or by those with chronic insomnia on an occasional basis.
Triazolam, sold under the brand name Halcion among others, is a central nervous system (CNS) depressant tranquilizer of the triazolobenzodiazepine (TBZD) class, which are benzodiazepine (BZD) derivatives. It possesses pharmacological properties similar to those of other benzodiazepines, but it is generally only used as a sedative to treat severe insomnia. In addition to the hypnotic properties, triazolam's amnesic, anxiolytic, sedative, anticonvulsant, and muscle relaxant properties are pronounced as well.
Carisoprodol, sold under the brand name Soma among others, is a medication used for musculoskeletal pain. Effects generally begin within half an hour and last for up to six hours. It is taken orally.
Zopiclone, sold under the brand name Imovane among others, is a nonbenzodiazepine, specifically a cyclopyrrolone, used to treat difficulty sleeping. Zopiclone is molecularly distinct from benzodiazepine drugs and is classed as a cyclopyrrolone. However, zopiclone increases the normal transmission of the neurotransmitter gamma-aminobutyric acid (GABA) in the central nervous system, via modulating GABAA receptors similarly to the way benzodiazepine drugs do inducing sedation but not with the anti-anxiety properties of the benzodiazepines.
Oxazepam is a short-to-intermediate-acting benzodiazepine. Oxazepam is used for the treatment of anxiety and insomnia and in the control of symptoms of alcohol withdrawal syndrome.
Fludiazepam, marketed under the brand name Erispan (エリスパン) is a potent benzodiazepine and 2ʹ-fluoro derivative of diazepam, originally developed by Hoffmann-La Roche in the 1960s. It is marketed in Japan and Taiwan. It exerts its pharmacological properties via enhancement of GABAergic inhibition. Fludiazepam has 4 times more binding affinity for benzodiazepine receptors than diazepam. It possesses anxiolytic, anticonvulsant, sedative, hypnotic and skeletal muscle relaxant properties. Fludiazepam has been used recreationally.
Etizolam is a thienodiazepine derivative which is a benzodiazepine analog. The etizolam molecule differs from a benzodiazepine in that the benzene ring has been replaced by a thiophene ring and triazole ring has been fused, making the drug a thienotriazolodiazepine.
Phenazepam is a benzodiazepine drug, first developed in the Soviet Union in 1975, and now produced in Russia and several other countries.
Meclonazepam ((S)-3-methylclonazepam) was discovered by a team at Hoffmann-La Roche in the 1970s and is a drug which is a benzodiazepine derivative similar in structure to clonazepam. It has sedative and anxiolytic actions like those of other benzodiazepines, and also has anti-parasitic effects against the parasitic worm Schistosoma mansoni.
Pyrazolam (SH-I-04) is a benzodiazepine derivative originally developed by a team led by Leo Sternbach at Hoffman-La Roche in the 1970s. It has since been "rediscovered" and sold as a designer drug since 2012.
Acetylfentanyl is an opioid analgesic drug that is an analog of fentanyl. Studies have estimated acetylfentanyl to be 15 times more potent than morphine, which would mean that despite being somewhat weaker than fentanyl, it is nevertheless still several times stronger than pure heroin. It has never been licensed for medical use and instead has only been sold on the illicit drug market. Acetylfentanyl was discovered at the same time as fentanyl itself and had only rarely been encountered on the illicit market in the late 1980s. However, in 2013, Canadian police seized 3 kilograms of acetylfentanyl. As a μ-opioid receptor agonist, acetylfentanyl may serve as a direct substitute for oxycodone, heroin or other opioids. Common side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea and potentially fatal respiratory depression. Fentanyl analogs have killed hundreds of people throughout Europe and the former Soviet republics since the most recent resurgence in use began in Estonia in the early 2000s, and novel derivatives continue to appear.
Diclazepam (Ro5-3448), also known as chlorodiazepam and 2'-chloro-diazepam, is a benzodiazepine and functional analog of diazepam. It was first synthesized by Leo Sternbach and his team at Hoffman-La Roche in 1960. It is not currently approved for use as a medication, but rather sold as an unscheduled substance. Efficacy and safety have not been tested in humans.
Flubromazepam is a benzodiazepine derivative which was first synthesized in 1960, but was never marketed and did not receive any further attention or study until late 2012 when it appeared on the grey market as a novel designer drug.
Flubromazolam (JYI-73) is a triazolobenzodiazepine (TBZD), which are benzodiazepine (BZD) derivatives. Flubromazolam is reputed to be highly potent, and concerns have been raised that clonazolam and flubromazolam in particular may pose comparatively higher risks than other designer benzodiazepines, due to their ability to produce strong sedation and amnesia at oral doses of as little as 0.5 mg. Life-threatening adverse reactions have been observed at doses of only 3 mg of flubromazolam.
Deschloroetizolam is a thienotriazolodiazepine that is the dechlorinated analog of the closely related etizolam. The compound has been sold as a designer drug.
Nifoxipam is a benzodiazepine that is a minor metabolite of flunitrazepam and has been sold online as a designer drug.
Bromazolam (XLI-268) is a triazolobenzodiazepine (TBZD) which was first synthesised in 1976, but was never marketed. It has subsequently been sold as a designer drug, first being definitively identified by the EMCDDA in Sweden in 2016. It is the bromo instead of chloro analogue of alprazolam and has similar sedative and anxiolytic effects to it and other benzodiazepines. Bromazolam is a non subtype selective agonist at the benzodiazepine site of GABAA receptors, with a binding affinity of 2.81 nM at the α1 subtype, 0.69 nM at α2 and 0.62 nM at α5. The "common" dosage range for users of bromazolam was reported to be 1–2 mg, suggesting its potency is similar to alprazolam.
Flunitrazolam is a triazolobenzodiazepine (TBZD), which are benzodiazepine (BZD) derivatives, that has been sold online as a designer drug, and is a potent hypnotic and sedative drug similar to related compounds such as flunitrazepam, clonazolam and flubromazolam. It was first definitively identified and reported to the EMCDDA Early Warning System, by an analytical laboratory in Germany in October 2016, and had not been described in the scientific or patent literature before this. It is the triazole analogue of Flunitrazepam (Rohypnol). The addition of the triazole ring to the scaffold increases potency significantly, this is evident as flunitrazolam is reported anecdotally to be active in the microgram level. It is active at 0.1 mg.
Flualprazolam is a tranquilizer of the triazolobenzodiazepine (TBZD) class, which are benzodiazepines (BZDs) fused with a triazole ring. It was first synthesised in 1976, but was never marketed. It can be seen as the triazolo version of fludiazepam. It has subsequently been sold as a designer drug, first being definitively identified as such in Sweden in 2018. It can be described as the 2'-fluoro derivative of alprazolam or the fluoro instead of chloro analogue of triazolam, and has similar sedative and anxiolytic effects.