Depressant


Depressants, also known as central nervous system depressants, or colloquially known as "downers", are a class of psychoactive drugs characterised by decreasing neurotransmission levels, decreasing the electrical activity of brain cells, or reducing arousal or stimulation in various areas of the brain. Commonly used depressants include alcohol, opioids, and benzodiazepines. Some specific depressants influence mood, either positively or negatively, but depressants often have no clear impact on mood. In contrast, stimulants, or "uppers", increase mental alertness, making stimulants the opposite drug class from depressants. Antidepressants are defined by their effect on mood, not on general brain activity, so they form an orthogonal category of drugs.
Depressants are closely related to sedatives as a category of drugs, with significant overlap. The terms may sometimes be used interchangeably or may be used in somewhat different contexts. Nearly all commonly used depressants are addictive, and use of them carries the risk of death from respiratory depression, especially in opioids.
Depressants are widely used throughout the world as prescription medicines and illicit substances. Alcohol is a very prominent depressant. When depressants are used, effects often include ataxia, anxiolysis, pain relief, sedation or somnolence, cognitive or memory impairment, as well as, in some instances, euphoria, dissociation, muscle relaxation, lowered blood pressure or heart rate, respiratory depression, and anticonvulsant effects. Depressants sometimes also act to produce anesthesia. Other depressants can include drugs like benzodiazepines and a number of opioids. Gabapentinoids like gabapentin and pregabalin are depressants and have anticonvulsant and anxiolytic effects. Most anticonvulsants, like lamotrigine and phenytoin, are depressants. Carbamates, such as meprobamate, are depressants that are similar to barbiturates. Anesthetics are generally depressants; examples include ketamine and propofol.
Depressants exert their effects through a number of different pharmacological mechanisms, the most prominent of which include facilitation of GABA and inhibition of glutamatergic or monoaminergic activity. Other examples are chemicals that modify the electrical signaling inside the body, the most prominent of which are bromides and channel blockers.

Indications

Depressants are used medicinally to relieve the following symptoms and disorders:

Alcohol

An alcoholic beverage is a drink that contains alcohol, an anesthetic that has been used as a psychoactive drug for several millennia. Ethanol is the oldest recreational drug still used by humans. Ethanol can cause alcohol intoxication when consumed. Alcoholic beverages are divided into three general classes for taxation and regulation of production: beers, wines, and spirits. They are legally consumed in most countries around the world. More than 100 countries have laws regulating their production, sale, and consumption.
The most common way to measure intoxication for legal or medical purposes is through blood alcohol content. It is usually expressed as a percentage of alcohol in the blood in units of mass of alcohol per volume of blood, or mass of alcohol per mass of blood, depending on the country. For instance, in North America, a blood alcohol content of 0.10 g/dL means that there are 0.10 g of alcohol for every dL of blood.

Barbiturates

Barbiturates were once popular treatments for insomnia, anxiety, and seizures, although their popularity has waned in recent decades. Barbiturates are sometimes used recreationally; they cause dependence and severe withdrawal, and they have a high risk of fatal overdose due to respiratory depression. By the late 1950s, concerns over the mounting social costs associated with barbiturates prompted a concerted effort to find alternative medications. Most people still using barbiturates today do so for the prevention of seizures or, in mild form, for relief from the symptoms of migraines. One barbiturate that remains in use for seizure disorders is phenobarbital.

Benzodiazepines

A benzodiazepine is a drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring. The first such drug, chlordiazepoxide, was discovered accidentally by Leo Sternbach in 1955 and made available in 1960 by Hoffmann–La Roche, which has also marketed the benzodiazepine diazepam since 1963.
Benzodiazepines enhance the effect of the neurotransmitter gamma-aminobutyric acid at the GABAA receptor, resulting in sedative, hypnotic, anxiolytic, anticonvulsant, and muscle relaxant properties. High doses of shorter-acting benzodiazepines induce anterograde amnesia, which may be helpful for surgical and procedural anesthesia to reduce patient recall. Midazolam is often used in anesthesiology. These properties make benzodiazepines useful in treating anxiety, insomnia, agitation, seizures, muscle spasms, alcohol withdrawal, and as a premedication for medical or dental procedures. Benzodiazepines are categorized as either short-, intermediate-, or long-acting. Short- and intermediate-acting benzodiazepines are preferred for the treatment of insomnia; longer-acting benzodiazepines are recommended for the treatment of anxiety.
In general, benzodiazepines are safe and effective in the short term, although cognitive impairments and paradoxical effects such as aggression or behavioral disinhibition occasionally occur. A minority of patients react to benzodiazepines with paradoxical agitation. Long-term use is controversial due to adverse psychological and cognitive effects, decreasing effectiveness, dependence, and benzodiazepine withdrawal syndrome, following withdrawal after long-term use. The elderly are at an increased risk of experiencing both short- and long-term adverse effects.
There is controversy concerning the safety of benzodiazepines in pregnancy. While they are not major teratogens, uncertainty remains as to whether they cause cleft palate in a small number of babies and whether neurobehavioral effects occur as a result of prenatal exposure; they are known to cause withdrawal symptoms in the newborn. Benzodiazepines can be overdosed and cause dangerous deep unconsciousness. However, they are much less toxic than their predecessors, barbiturates, and death rarely results when a benzodiazepine is the only drug taken; however, when combined with other central nervous system depressants such as alcohol and opioids, the potential for toxicity and fatal overdose increases. Benzodiazepines are commonly misused and taken in combination with other addictive drugs. In addition, all benzodiazepines are listed in the Beers List, which is significant in clinical practice.

Cannabis

is often considered either in its own unique category or as a mild psychedelic. The chemical compound tetrahydrocannabinol, which is found in cannabis, has many depressant effects, such as muscle relaxation, sedation, decreased alertness, and drowsiness. Contrarily, activation of the CB1 receptor by cannabinoids causes an inhibition of GABA, which is atypical to most other depressants.

Carbamates

s are a class of depressants, or "tranquilizers", that are synthesized from urea. Carbamates have anxiolytic, muscle relaxant, anticonvulsant, hypnotic, antihypertensive, and analgesic effects. They have other uses, like muscle tremors, agitation, and alcohol withdrawal. Their muscle relaxant effects are useful for strains, sprains, and muscle injuries combined with rest, physical therapy, and other measures. The effects, synthesis, and mechanism of action of carbamates are very similar to those of barbiturates.
Side effects of carbamates include drowsiness, dizziness, headache, diarrhea, nausea, flatulence, liver failure, poor coordination, nystagmus, abuse, dizziness, weakness, nervousness, euphoria, overstimulation, and dependence. Uncommon but potentially severe adverse reactions include hypersensitivity reactions such as Stevens–Johnson syndrome, embryo-fetal toxicity, stupor, and coma. It is not recommended to use most carbamates, like carisoprodol, for a long time, as physical and psychological dependence do occur.
Meprobamate was launched in 1955. It quickly became the first popular psychotropic drug in America, becoming popular in Hollywood and gaining fame for its seemingly miraculous effects. It has since been marketed under more than 100 trade names, including Amepromat, Quivet, and Zirpon. Carisoprodol, which metabolizes into meprobamate and is still used mainly for its muscle relaxant effects, can potentially be abused. Its mechanism of action is very similar to that of barbiturates, alcohol, methaqualone, and benzodiazepines. Carisoprodol allosterically modulates and directly activates the human α1β2γ2 GABAAR in the central nervous system, similar to barbiturates. This causes chloride channels to open, allowing chloride to flood into the neuron. This slows down communication between neurons and the nervous system. Unlike benzodiazepines, which increase the frequency of the chloride channel opening, carisoprodol increases the duration of channel opening when GABA is bound. GABA is the main inhibitory neurotransmitter in the nervous system, which causes its depressant effects.
Carbamates are fatal in overdose, which is why many have been replaced with benzodiazepines. Symptoms are similar to a barbiturate overdose and typically include difficulty thinking, poor coordination, decreased levels of consciousness, and a decreased effort to breathe. An overdose is more likely to be fatal when mixed with another depressant that suppresses breathing.
Physical and psychological dependence does happen with long-term use of carbamates, particularly carisoprodol. Today, carisoprodol is only used in the short term for muscle pain, particularly back pain. Discontinuation after long-term use could be very intense and even possibly fatal. Withdrawal can resemble barbiturate, alcohol, or benzodiazepine withdrawal, as they all have a similar mechanism of action. Discontinuation symptoms include confusion, disorientation, delirium, hallucinations, insomnia, decreased appetite, anxiety, psychomotor agitation, pressured speech, tremor, tachycardia, and seizures, which could be fatal.
Carbamates gained widespread use in the 1950s, alongside barbiturates. While their popularity has gradually waned due to concerns over overdose and dependence potential, newer derivatives of carbamates continue to be developed. Among these is Felbamate, an anticonvulsant that was approved in 1993 and is commonly used today. It is a GABAA positive allosteric modulator and blocks the NR2B subunit of the NMDA receptor. Other carbamates block sodium channels. Phenprobamate was used as an anxiolytic and is still sometimes used in Europe for general anesthesia and for treating muscle cramps and spasticity. Methocarbamol is a popular drug that is commonly known as Robaxin and is over-the-counter in some countries. It is a carbamate with muscle relaxant effects. Tetrabamate is a controversial drug that is a combination of febarbamate, difebarbamate, and phenobarbital. It is marketed in Europe and has been largely, but not completely, discontinued. On 4 April 1997, after over 30 years of use due to reports of hepatitis and acute liver failure, the use of the drug was restricted. Carisoprodol, known as "Soma", is still commonly used today for its muscle relaxant effects. It is also very commonly abused around the world. It is a Schedule IV substance in the United States.
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