Diclazepam

IUPAC Name

7-chloro-5-(2-chlorophenyl)-1-methyl-3H-1,4-benzodiazepin-2-one

Year(s) and type of review / ECDD meetings
Drug Class
Technical information (most recent pre-review / critical review report)
ECDD Recommendation
Inclusion in Schedule IV of the 1971 Convention on Psychotropic Substances
Recommendation (from TRS)

Substance identification
Diclazepam (chemical name: 7-chloro-5-(2-chlorophenyl)-1-methyl-1,3- dihydro-2H-benzo[e][1,4]diazepin-2-one) is a 2-chloro derivative of the benzodiazepine diazepam. It is found as a white powder, and is commonly sold as tablets, pellets and liquid.

WHO review history
Diclazepam has not been formally reviewed by WHO and is not currently under international control. Information was brought to WHO’s attention that this substance is manufactured clandestinely, poses a risk to public health and has no recognized therapeutic use.

Similarity to known substances and effects on the central nervous system
Diclazepam is an agonist at the benzodiazepine site of the GABAA receptor, acting to increase the effect of the inhibitory neurotransmitter GABA. Diclazepam has effects similar to those of the benzodiazepine diazepam, which is currently controlled under the Convention on Psychotropic Substances of 1971. It is metabolized to the benzodiazepines delorazepam, lorazepam and lormetazepam, which are active and are also pharmaceuticals included in Schedule IV of the Convention on Psychotropic Substances of 1971.

Diclazepam was shown to cause sedation and muscle relaxation in animals. Central nervous system depressant effects have been described in humans.

Dependence potential
No controlled studies have been reported in animals or humans on the dependence potential of diclazepam. Online user reports describe cross-tolerance with other benzodiazepines and use to self-manage benzodiazepine withdrawal. This evidence and its mechanism of action suggest that diclazepam can produce dependence, like other benzodiazepines.

Actual abuse and/or evidence of likelihood of abuse
No controlled studies in animals or humans have been reported on the abuse liability of diclazepam. On the basis of its mechanism of action and its effects, however, its abuse liability would be expected to be similar to that of other benzodiazepines.

Diclazepam has the potential to increase unintentional opioid overdoses. Its long half-life may increase the risk of accumulation and of interactions when combined with other drugs. Fatal intoxication with diclazepam has been reported.

Seizures have been reported with diclazepam in many countries in various regions. Diclazepam is increasingly being sold as falsified benzodiazepines, commonly as diazepam.

Diclazepam has been implicated in cases of impaired driving, including when it was identified as the main contributor to impairment. It also has been involved in cases of drug-facilitated sexual assault.

Therapeutic usefulness
Diclazepam is not known to have any therapeutic use, is not on the WHO Model List of Essential Medicines and has never been marketed as a medicinal product.

Recommendation
Diclazepam (chemical name: 7-chloro-5-(2-chlorophenyl)-1-methyl-1,3- dihydro-2H-benzo[e][1,4]diazepin-2-one) is a 2-chloro analogue of the benzodiazepine diazepam, with actions and effects very similar to those of benzodiazepines listed under Schedule IV of the Convention on Psychotropic Substances of 1971. It can produce a state of dependence and central nervous system depression, like other benzodiazepines. There have been reports of abuse, impaired driving and fatal and nonfatal intoxications. There is sufficient evidence of its abuse to conclude that it constitutes a significant risk to public health; it has no known therapeutic use.

Recommendation: The Committee recommended that diclazepam (chemical name: 7-chloro-5-(2-chlorophenyl)-1-methyl-1,3-dihydro-2H-1,4- benzodiazepin-2-one) be added to Schedule IV of the 1971 Convention on Psychotropic Substances.