Sedatives encompass a wide variety of drugs with different mechanisms of action that can induce depression of the central nervous system (CNS). In the first part of the 20th century, the pharmacotherapy of anxiety and insomnia relied on barbiturates, which were replaced with benzodiazepines as drugs of choice in the second part of the previous century. Besides those two groups of drugs, other sedatives are also used for that purpose.
Barbiturates and benzodiazepines
Barbiturates are nonselective CNS depressants that used to be the mainstay of treatment to sedate patients or to induce and maintain sleep. In modern medicine they have been largely replaced by the benzodiazepines, primarily because they can induce tolerance, physical dependence and serious withdrawal symptoms. Nevertheless, certain barbiturates are still employed as anticonvulsants (phenobarbital) and to induce anesthesia (thiopental). The representatives of this group are:
- Amobarbital (Amytal)
- Aprobarbital (Alurate)
- Butabarbital (Butisol)
- Mephobarbital (Mebaral)
- Methohexital (Brevital)
- Pentobarbital (Nembutal)
- Phenobarbitol (Luminal)
- Primidone (Mysoline)
- Secobarbital (Seconal)
- Thiopental (Penothal)
Benzodiazepines are the most widely used group of sedative drugs. Due to their safety and improved effectiveness, they have largely replaced barbiturates as drugs of choice in the treatment of anxiety. They also have hypnotic, anticonvulsant and muscle-relaxing activities, but do not exhibit analgesic action or antipsychotic activity. The representatives of this group are:
- Alcohol (ethyl alcohol or ethanol)
- Alprazolam (Xanax)
- Chloral hydrate (Somnote)
- Chlordiazepoxide (Librium)
- Clorazepate (Tranxene)
- Clonazepam (Klonopin)
- Diazepam (Valium)
- Estazolam (Prosom)
- Flunitrazepam (Rohypnol)
- Flurazepam (Dalmane)
- Lorazepam (Ativan)
- Midazolam (Versed)
- Nitrazepam (Mogadon)
- Oxazepam (Serax)
- Temazepam (Restoril)
- Triazolam (Halcion)
Other sedatives
Nonbenzodiazepine “Z-drugs” sedative-hypnotics are drugs that differ in structure from benzodiazepines, but acts on a subset of the benzodiazepine receptor family known as BZ1. Their onset of action is rapid, and they are considered the preferred hypnotics as they do not significantly alter the various sleep stages due to their relative selectivity for the aforementioned receptor. The representatives of this group are:
- Eszopiclone (Lunesta)
- Zaleplon (Sonata)
- Zolpidem (Ambien)
- Zopiclone (Zimovane)
Certain antihistamines with sedating properties (also known as first-generation antihistamines) are effective in treating mild forms of insomnia, although numerous undesirable side effects (such as their anticholinergic properties) make them less useful in comparison with benzodiazepines. Some sedative antihistamines can be found in numerous over-the-counter products. The representatives of this group are:
- Chlorpheniramine (Histafen)
- Dexchlorpheniramine (Polaramine)
- Dimenhydrinate (Dramamine)
- Diphenhydramine (Benadryl)
- Promethazine (Phenergan)
- Trimeprazine (Vallergan Forte)
Herbal sedatives have been used all over the world to treat insomnia and anxiety for thousands of years. Although they are undoubtedly effective to certain extent, some aspects of their psychopharmacology have to be resolved; for example, there is poor in vivo evidence of pharmacodynamics in humans, problematic efficacy evaluation in clinical studies, as well as cumbersome production of standardized extracts and lack of bioequivalence between different extracts. The representatives of this group are:
- Atractylodes macrocephala
- Dimocarpus longan
- Dorstenia arifolia
- Ipomoea tyrianthina
- Hypericum montbretii
- Piper methysticum
- Valeriana officinalis
- Zizyphus jujuba Mill var. spinosa
Other sedatives include alcohol, opioid sedatives, anesthetics, carbinols, agonists of melatonin receptors and other medicines that also act as CNS depressants via different mechanisms. They usually have limited therapeutic use, and some of the representatives are:
- Chloral hydrate (Aquachloral)
- Dexmedetomidine (Precedex)
- Ethchlorvynol (Placidyl)
- Etomidate (Amidate)
- Glutethimide (Doriden)
- Methyprylon (Nodular)
- Meprobamate (Miltown)
- Methaqualone (Quaalude)
- Paraldehyde (Paral)
- Propofol (Diprivan)
- Ramelteon (Rozerem)
- Dexmedetomidine (Precedex)
Further Reading