Clonazepam
Clonazepam (5-(2-chlorophenyl)-1,3-dihydro-7 nitro-2H-1,4-benzodiazepin-2-one) is an anti-convulsant benzodiazepine and it displays many of the effects common to all benzodiazepines. It is available in tablets containing 0.5 mg, 1 mg and 2 mg under the trade names Klonopin™, Clonex™, Iktorivil™ and Rivotril™. It is a CNS depressant that results in loss of voluntary muscle control and loss of inhibition, and reduces anxiety. Like some other benzo diazepines, it causes anterograde amnesia. Clonazepam is metabolised in the liver to 7-aminoclonazepam by reduction of the 7-nitro group (Figure 1). This is followed by hydroxyl ation at the 3-carbon and subsequent glucuronidation. Almost all of the parent drug is metabolised – less than 0.5% of clonazepam is excreted unchanged in the urine. The elimination half-life from plasma has been described as being between 19 and 60 hours. The apparent volume of distribution ranges between 1.5 and 6.2 L/kg. After a 2 mg dose of clonazepam, the peak concentration of both parent compound and 7-aminoclonazepam in blood occurs 2 hours after ingestion. The onset of action of clonazepam is between 30 and 60 minutes, and duration of action may last up to 12 hours. Clonazepam is a highly potent benzodiazepine with a relatively low affinity for the benzodiazepine receptor. It must cross the blood–brain barrier to get to its site of action. The ability of a drug to cross this barrier depends on protein binding, lipid solubility and ionisation constant. Clonazepam is largely non-ionised at physiological pH and relatively water insoluble, so it readily crosses biological membranes and therefore rapidly passes from the blood to the brain. It has also been shown to decrease seizure activity and is approved by the Food and Drug Administration only for use in the treatment of seizures. Clonazepam is a DEA Schedule IV drug, available by prescription in the USA.
Owing to the physiological effects after clonazepam ingestion, it has the potential to be abused in drug-facilitated sexual assault situations. Clonazepam causes decreased inhibition, reduced anxiety, and a loss of voluntary muscle control. In addition, it causes anterograde amnesia, impairing the victim’s memory of events occurring shortly after ingestion of the drug. These qualities may make clonazepam attractive to potential sexual offenders. Another fact that makes clonazepam particularly dangerous as a date-rape drug is that it is sometimes sold under the same street name ‘Roofies’ as flunitrazepam.
Figure 1 Chemical structure of clonazepam and its major metabolite 7-aminoclonazepam.
