Diclazepam

Diclazepam, also known as 2-chlorodiazepam or Ro5-3448, is a synthetic benzodiazepine structurally related to diazepam. It was synthesised in the 1960s but was never marketed as a medicine. Diclazepam appeared on the research-chemical market in the 2010s and has been found in counterfeit diazepam products. It is long acting and is metabolised into several active benzodiazepines, including delorazepam, lorazepam and lormetazepam.

Chemistry and history

Diclazepam is a 2′-chloro derivative of diazepam. Its structure contains the conventional benzodiazepine ring system, with an additional chlorine substituent on the phenyl ring. It was first synthesised by Leo Sternbach and colleagues at Hoffmann-La Roche in 1960, but it did not become an approved pharmaceutical product.

The compound was reported to European monitoring authorities in 2013 and later appeared in online research-chemical markets. It has also been identified in tablets sold as diazepam, making the name on a product an unreliable guide to its actual contents.

Pharmacology and metabolism

Diclazepam acts at the benzodiazepine site of the GABA_A receptor, enhancing the inhibitory action of GABA. Its effects are broadly similar to diazepam and include anxiolytic, sedative, hypnotic and muscle-relaxant activity.

A human self-experiment and analytical study found an elimination half-life of approximately 42 hours. Diclazepam is metabolised into the active benzodiazepines delorazepam, lorazepam and lormetazepam. These metabolites can remain detectable in biological samples after the parent compound has declined (Moosmann and colleagues, 2014).

Subjective effects

The PsychonautWiki profile of diclazepam describes effects similar to diazepam, including anxiety suppression, muscle relaxation, sedation and memory impairment. This comparison rests on anecdotal reports, not clinical evidence.

Physical effects

Sedation and muscle relaxation are commonly reported. Other effects include dizziness, reduced motor coordination and, in more severe intoxication, respiratory depression. The long persistence of the parent compound and its active metabolites can make impairment difficult to assess from the time of exposure alone.

Cognitive effects

Reported effects include reduced anxiety, disinhibition, sleepiness and memory suppression. Some accounts describe a hypnotic effect without pronounced euphoria. Confusion and impaired judgement can occur, while the subjective sense of being unimpaired may not match actual psychomotor performance.

Clinical and forensic findings

Clinical reports describe both central nervous system depression and withdrawal symptoms. Diclazepam has been detected in impaired-driving investigations, including cases where it was considered a major contributor to impairment. It has also been identified in investigations of drug-facilitated sexual assault.

The WHO review notes that diclazepam has been found in counterfeit diazepam products and that its long half-life may increase the risk of accumulation and interactions. Fatal and non-fatal intoxications have been reported, often alongside other psychoactive substances (WHO critical review summary).

Dependence and withdrawal

There are no controlled studies that quantify diclazepam dependence, but its pharmacology is consistent with the benzodiazepine class. User reports describe cross-tolerance with other benzodiazepines and the use of diclazepam to manage withdrawal from other substances. Such reports cannot establish its safety or suitability as a withdrawal treatment.

Regular benzodiazepine use can lead to physical dependence. Abrupt discontinuation after dependence has developed may cause severe withdrawal, including seizures, and should not be attempted without medical guidance.

Related compounds

Diclazepam is closely related to Diazepam and is metabolised into Delorazepam, Lorazepam and Lormetazepam. These relationships are important when interpreting toxicology results because the metabolites may remain detectable longer than the parent compound.