Ethchlorvynol is a GABA-ergic

sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but t ...

and

hypnotic Hypnotic (from Greek ''Hypnos'', sleep), or soporific drugs, commonly known as sleeping pills, are a class of (and umbrella term for) psychoactive drugs whose primary function is to induce sleep (or surgical anesthesiaWhen used in anesthesia ...

soporific Hypnotic (from Greek ''Hypnos'', sleep), or soporific drugs, commonly known as sleeping pills, are a class of (and umbrella term for) psychoactive drugs whose primary function is to induce sleep (or surgical anesthesiaWhen used in anesthesia ...

medication first developed by

Pfizer Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfizer ...

in the 1950s. In the United States it was sold by

Abbott Laboratories Abbott Laboratories is an American multinational medical devices and health care company with headquarters in Abbott Park, Illinois, United States. The company was founded by Chicago physician Wallace Calvin Abbott in 1888 to formulate known dr ...

under the trade name Placidyl. Placidyl was available in 200 mg, 500 mg, and 750 mg strength gel filled capsules. While the 500 mg and 750 mg strength capsules were for use in reducing sleep latency, the 200 mg strength capsules were intended to be used to re-induce sleep in case of early awakening. Abbott discontinued production in 1999, due to it being replaced by the

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...

family and its widespread abuse, after which Placidyl was available for about a year in the United States. Although, theoretically, ethchlorvynol could be manufactured for sale in the United States by another pharmaceutical company (subject to FDA approval of such manufacture), no pharmaceutical company has chosen to do so. Individuals with a valid prescription for the substance may legally transport a reasonable amount of ethclorvynol with them into the United States.

Use and effects

Ethchlorvynol was used to treat

insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

, but prescriptions for the drug had fallen significantly by 1990, as other hypnotics that were considered safer (i.e., less dangerous in overdose) became much more common. It is no longer prescribed in the United States due to unavailability, but it is still available in some countries and would still be considered legal to possess and use with a valid prescription. Along with expected sedative effects of relaxation and drowsiness, adverse reactions to ethchlorvynol include skin rash, faintness, restlessness and

euphoria Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and da ...

. Early adjustment side effects may include nausea and vomiting, numbness, blurred vision, stomach pains and temporary dizziness. There are no specific antidotes available for ethchlorvynol, and treatment is supportive with protocols resembling those for the treatment of

barbiturate overdose Barbiturate overdose is poisoning due to excessive doses of barbiturates. Symptoms typically include difficulty thinking, poor coordination, decreased level of consciousness, and a decreased effort to breathe ( respiratory depression). Complica ...

. Overdose may be marked by a variety of symptoms, including confusion, fever,

peripheral A peripheral or peripheral device is an auxiliary device used to put information into and get information out of a computer. The term ''peripheral device'' refers to all hardware components that are attached to a computer and are controlled by the ...

numbness and weakness, reduced coordination and muscle control, slurred speech, reduced heartbeat, respiratory depression, and in extreme overdoses, coma and death. As with all

GABAA receptor The GABAA receptor (GABAAR) is an ionotropic receptor and ligand-gated ion channel. Its endogenous ligand is γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Upon opening, the GABAA receptor on ...

agonists, Placidyl can be habit forming and extremely physically addictive (with potentially lethal withdrawal resembling

delirium tremens Delirium tremens (DTs) is a rapid onset of confusion usually caused by withdrawal from alcohol. When it occurs, it is often three days into the withdrawal symptoms and lasts for two to three days. Physical effects may include shaking, shiver ...

and

benzodiazepine withdrawal Benzodiazepine withdrawal syndrome often abbreviated to benzo withdrawal or BZD withdrawal is the cluster of signs and symptoms that may emerge when a person who has been taking benzodiazepines, either medically or recreationally develops a phy ...

). After prolonged use, withdrawal symptoms may include convulsions, hallucinations, and

amnesia Amnesia is a deficit in memory caused by brain damage or disease,Gazzaniga, M., Ivry, R., & Mangun, G. (2009) Cognitive Neuroscience: The biology of the mind. New York: W.W. Norton & Company. but it can also be caused temporarily by the use ...

. As with most hypnotics, Placidyl was indicated for use in the treatment of insomnia for a short period of time (a week or two). However, it was nonetheless not uncommon for doctors to prescribe Placidyl (and other hypnotics) for extended periods of time, as currently prescribed soporifics are today. During the late 1970s, ethchlorvynol was sometimes over-prescribed causing a minor epidemic of persons who quickly became addicted to this powerful drug.

Elvis Presley Elvis Aaron Presley (January 8, 1935 – August 16, 1977), or simply Elvis, was an American singer and actor. Dubbed the "Honorific nicknames in popular music, King of Rock and Roll", he is regarded as Cultural impact of Elvis Presley, one ...

was quite fond of Placidyl, Supreme Court Justice

William Rehnquist William Hubbs Rehnquist ( ; October 1, 1924 – September 3, 2005) was an American attorney and jurist who served on the U.S. Supreme Court for 33 years, first as an associate justice from 1972 to 1986 and then as the 16th chief justice from ...

had to be hospitalized for detox of Placidyl, as was

Steven Tyler Steven Victor Tallarico (born March 26, 1948), known professionally as Steven Tyler, is an American singer, best known as the lead singer of the Boston-based rock band Aerosmith, in which he also plays the harmonica, piano, and percussion. ...

of Aerosmith. Occasional deaths would occur when addicted persons would try to inject the drug directly into a vein or an artery. Ethchlorvynol is not compatible with

intravenous injection Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutri ...

and serious injury (including the loss of limbs due to vascular injury) or death can occur when it is used in this manner.

Chemistry

Ethchlorvynol is a member of the class of sedative-hypnotic carbinols, which includes methylparafynol and ''tert''-amyl alcohol. It is not a

carbamate In organic chemistry, a carbamate is a category of organic compounds with the general formula and structure , which are formally derived from carbamic acid (). The term includes organic compounds (e.g., the ester ethyl carbamate), formally o ...

, or barbituric acid derivative, and its molecular structure is considerably simpler. The systematic name of ethchlorvynol is usually given as ethyl 2-chlorovinyl ethynyl carbinol or 1-chloro-3-ethylpent-1-en-4-yn-3-ol. Its empirical formula is C₇H₉ClO. Ethchlorvynol is synthesized by an ethynylation reaction using lithium

acetylide In organometallic chemistry, acetylide refers to chemical compounds with the chemical formulas and , where M is a metal. The term is used loosely and can refer to substituted acetylides having the general structure (where R is an organic side c ...

and 1-chloro-1-penten-3-one in

liquid ammonia Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous wast ...

, followed by acidic work-up. : Ethchlorvynol synthesis

The analogous compound consisting of a

derived from the

hydroxyl group In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy g ...

was investigated and was shown to have a slower onset, longer duration, and increased potency, but was not developed commercially.

References

External links

* {{GABAAR PAMs Withdrawn drugs Tertiary alcohols Ethynyl compounds AbbVie brands Sedatives GABAA receptor positive allosteric modulators Haloalkenes Organochlorides