Benzodiazepine-like drugs

Woods, J.H., Katz, J.L. and Winger, G. (1995) Abuse and Therapeutic Use of Benzodiazepines and Benzodiazepine-like Drugs in Psychopharmacology The Fourth Generation of Progress (Kupfer, F.E., Bloom, D.J., eds.) pp. 1777-1791, Raven Press, New York. 

Rowlett JK, Platt DM, Lelas S, et al. Different GABAa receptor subtypes mediate the anxiolytic, abuse-related, and motor effects of benzodiazepine-like drugs in primates. Proc Natl Acad Sci L) S A 2005 102 915-920. 

Visual hallucinations lasting 3 to 4 hours occurred in a 17-year-oid boy who had been taking bupropion 450 mg daiiy for one month and zolpidem 5 to 10 mg daily for about 6 months, when he increased the zolpidem dose to 60 mg. Note that the recommended dose of zolpidem is 10 mg daily and that zolpidem itself can cause psychiatric adverse effects such as hallucinations. Therefore an interaction is not established. Bupropion is contraindicated during abrupt withdrawal from any drug known to be associated with seizures on withdrawal, particularly benzodiazepines and benzodiazepine-like drugs. ... 

HYPNOSEDATIVES AND BENZODIAZEPINE-LIKE DRUGS (SED-15,3710 SEDA-33, 78 SEDA-34, 47]... 

Because Rohypnol is banned in the United States, there is an emerging trend for young people to start abusing two other Rohypnol-like drugs that are still legal in the United States clonazepam (Klonopin ) and alprazolam (Xanax). Both Klonopin and Xanax are benzodiazepines that are used for the treatment of anxiety and insomnia. Although they are less potent than Rohypnol, they can produce similar effects when mixed with alcohol and also have been reported to enhance the effects of heroin. 

Withdrawal reactions are more problematical. Hypnotics, by and large, are benzodiazepine like in their pharmacology, receptor binding, etc. The main differences relate to duration of action and to putative selectivity of binding. The benzodiazepine withdrawal reaction has been described many times, and rating scales have been developed to measure the symptoms. Withdrawal reactions from hypnotics would be expected to display similar symptomatic patterns and to follow time-courses dictated by the pharmacokinetic properties of the drug. 

Until about 1980, it was widely accepted that the benzodiazepine structure was a prerequisite for the anxiolytic profile and for the recognition of and binding to the benzodiazepine receptor. More recently, however, a chemically unrelated drug, the cyclopyrrolone zopiclone, has been shown to be a useful sedative hypnotic with a benzodiazepine-like profile. Other chemical classes of drugs that are also structurally dissimilar to the benzodiazepines (e.g. triazolopyridazines) have also been developed and shown to have anxiolytic activity in man these non-benzodiazepines also act via the benzodiazepine receptor. Thus the term "benzodiazepine receptor ligand" has been introduced to describe all drugs, irrespective of their chemical structure, that act on benzodiazepine receptors and thereby modulate inhibitory transmission in the brain. 

Although many health care providers have been misled by drug company promotional efforts, the great majority of sleep aids share the same risks as the BZs (see the appendix for a list). Almost all are placed in Schedule IV by the DEA to indicate a risk of abuse and dependence. According the DEA (2006), Ambien and Sonata (zaleplon) are benzodiazepine-like CNS depressants. ... 

Antidepressant drugs of various classes (tricyclics, monoamine oxidase inhibitors, SSRIs) have broad efficacy in generalized anxiety and in panic disorder, for which they are the treatments of choice (6,7). While not likely to cause benzodiazepine-like dependence or abuse, they do have a significant therapeutic latency, and the older drugs are very toxic in overdose. 

Sedative-hypnotic drugs and anxiolytic drugs are CNS depressants that are used medically to reduce anxiety and/or induce sleep. They may also be used as anticonvulsants. Phenobarbital, for example, is often the maintenance drug of choice for seizure-prone individuals. In general, the sedative-hypnotic family of drugs includes alcohol, barbiturates, benzodiazepines, and such barbiturate-like drugs as chloral hydrate, glutethi-mide, meprobamate, and methaqualone. 

Benzodiazepines, like most lipid-soluble drugs, undergo biotransformation to more water-soluble glucuronide compounds, which are eventually eliminated in the urine. The primary metabolites of diazepam (N-desmethyldiazepam) and midazolam (a-hydroxymidazolam) are pharmacologically active, with similar potency to their parent compounds. These active metabolites are probably of little clinical significance after i.v. administration, because of their rapid elimination and the significance of redistribution in the termination of the CNS effect. 

Hypnotic doses of barbiturates increase the total sleep time and alter the stages of sleep in a dose-dependent manner. Like the benzodiazepines, these drugs decrease sleep latency, the number of awakenings, and the durations of rapid-eye-movement (REM) and slow-wave sleep. During repetitive nightly administration, some tolerance to the effects on sleep occurs within a few days, and the effect on total sleep time may be reduced by as much as 50% after 2 weeks of use. Discontinuation leads to rebound increases in all the parameters reported to be decreased by barbitmates. 

Mania, delusions, hallucinations, paranoia, aggressive behavior, schizophrenic relapse, depression, anxiety See Antidepressants, tricyclic See Benzodiazepines See Amphetamine-like drugs Nightmares, confusion, paranoia, depression, visual hallucinations Depression, suicidal thoughts Hallucinations, paranoia, panic, depression... 

There is some evidence of a synergistic effect on reinforcement with concurrent administration of benzodiazepines and opioids (Walker and Ettenberg 2003). Cocaine abusers are less likely than opioid abusers to abuse benzodiazepines, preferring alcohol and opioids as secondary drugs of abuse. The most common pattern of benzodiazepine misuse in these individuals is intermittent use of therapeutic or supratherapeutic doses to counter unwanted effects of cocaine. 

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