ethchlorvynol
{{Short description|Group of stereoisomers}}
{{Use dmy dates|date=September 2022}}
{{infobox drug
| Verifiedfields = changed
| verifiedrevid = 408562693
| IUPAC_name = 1-chloro-3-ethylpent-1-en-4-yn-3-ol
| image = Ethchlorvynol.svg
| image_class = skin-invert-image
| alt = Structural formula
| image2 = Ethchlorvynol molecule ball.png
| alt2 = Ball-and-stick model of the ethchlorvynol molecule
| width = 190
| pronounce = {{IPAc-en|ˌ|ɛ|θ|k|l|ɔːr|ˈ|v|aɪ|n|ɒ|l}}
{{respell|ETH|klor|VY|nol}}
| Drugs.com = {{drugs.com|CONS|ethchlorvynol}}
| pregnancy_category =
| legal_BR = B1
| legal_BR_comment = {{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=Diário Oficial da União |language=pt-BR |publication-date=2023-04-04}}
| legal_CA = Schedule IV
| legal_DE = Anlage II
| legal_US = Schedule IV
| legal_UK = Class C
| legal_US_comment = {{cite web | url=http://www.incb.org/documents/Psychotropics/forms/P/P_ENG_2013_85229_GHB.pdf | archive-url = https://web.archive.org/web/20150910065423/http://www.incb.org/documents/Psychotropics/forms/P/P_ENG_2013_85229_GHB.pdf | archive-date = 10 September 2015 | title = Annual Statistical Report on Substances Listed in the Convention on Psychotropic Substances of 1971 Form P | publisher= International Narcotics Control Board (INCB) | date=January 2014 | access-date=17 April 2014 | pages=9}}
| routes_of_administration = Oral
| bioavailability =
| protein_bound = 35–50%
| metabolism =
| elimination_half-life =
| IUPHAR_ligand = 7180
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 113-18-8
| ATC_prefix = N05
| ATC_suffix = CM08
| ATC_supplemental =
| PubChem = 5281077
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank = DB00189
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4444534
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 6EIM3851UZ
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00704
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 591
| C=7 | H=9 | Cl=1 | O=1
| smiles = Cl[C@H]=CC(C#C)(O)CC
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C7H9ClO/c1-3-7(9,4-2)5-6-8/h1,5-6,9H,4H2,2H3/b6-5+
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = ZEHYJZXQEQOSON-AATRIKPKSA-N
}}
Ethchlorvynol is a GABA-ergic hypnotic sedative medication first developed by Pfizer in the 1950s.{{cite patent | country = US | number = 2746900 | gdate = 1956 | title = Hypnotic Agent and Method of Making the Same | invent1 = Bavley A, McLamore WM }} In the United States, it was sold by Abbott Laboratories under the trade name Placidyl.{{cite web | url=https://www.erowid.org/pharms/ethchlorvynol/ethchlorvynol.shtml | title=Erowid Ethchlorvynol Vault | publisher=Erowid | date=12 January 2007 | access-date=17 April 2014}} 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 problems of the widespread abuse of minor tranquilizers, and non-barbiturate sedatives largely being replaced by the benzodiazepine family (with drugs such as Librium and Valium);{{Cite book |last=Giannini |first=A. James |url=https://archive.org/details/drugsofabuse0000gian |title=Drugs of abuse |date=15 January 1997 |publisher=Practice Management Information Corp. |isbn=9781570660535 |edition=2nd |location=Los Angeles, California |pages=147 |language=En |lccn=96024680 |oclc=34906127 |ol=986590M |access-date=21 May 2025}} by the end of 2001, ethchlorvynol reserves had dried up in the United States.
Theoretically, ethchlorvynol could be manufactured for sale in the United States by another pharmaceutical company (subject to FDA approval of such manufacture), though 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. The availability of ethchlorvynol resembles similar barbiturate-like, GABA-ergic sedatives, such as glutethimide (Doriden, which ceased production in U.S. by 1993), ethinamate (Valmid), and methyprylon (vended as Noludar, Noctan, and Dimerin), which were voluntarily withdrawn in favor of benzodiazepine hypnotics in 1965, and supplies widely eliminated by 1969. These are all controlled substances, but are not illegal. Equivalent alertness-promoting medications with a similar case include mefenorex, phenmetrazine, and phendimetrazine.
Use and effects
Ethchlorvynol was indicated to treat insomnia, and was widely prescribed in the 1960s and 1970s; prescriptions had fallen significantly by 1990, however, as other hypnotics that were considered safer and less dangerous in overdose became more common.
=Availability=
Ethchlorvynol is no longer prescribed in the United States due to unavailability, but 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. 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. Overdose may be marked by a variety of symptoms, including confusion, fever, peripheral 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 agonists, ethchlorvynol can be habit-forming and severely physically addictive; abrupt cessation of long-term use of this and similar substances can result in potentially lethal withdrawal effects resembling delirium tremens (from alcohol withdrawal), benzodiazepine withdrawal, or barbiturate withdrawal, including convulsions, hallucinations, and amnesia. As with most hypnotics, Placidyl was indicated for use in the treatment of insomnia for a short period of time, generally ranging from one week to one month. However, it was not uncommon for doctors to prescribe the medication for extended periods of time. In the late 1970s, ethchlorvynol was deemed responsible as one of the agents responsible for the death of Elvis Presley, and resulted in Supreme Court Justice William Rehnquist as well as Steven Tyler of Aerosmith both being hospitalized for detox. 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, and serious injury (including the loss of limbs due to vascular injury) or death can occur when it is used in this manner.{{cite journal | vauthors = Glauser FL, Smith WR, Caldwell A, Hoshiko M, Dolan GS, Baer H, Olsher N | title = Ethchlorvynol (Placidyl)-induced pulmonary edema | journal = Annals of Internal Medicine | volume = 84 | issue = 1 | pages = 46–8 | date = January 1976 | pmid = 942681 | doi = 10.7326/0003-4819-84-1-46 }}
Chemistry
Ethchlorvynol is a member of the class of sedative-hypnotic carbinols, which includes methylparafynol and tert-amyl alcohol. It is not a benzodiazepine, carbamate, or barbiturate, 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.{{citation needed|date=November 2024}} Its empirical formula is C7H9ClO.
Ethchlorvynol is synthesized by an ethynylation reaction using lithium acetylide and 1-chloro-1-penten-3-one in liquid ammonia, followed by acidic work-up.{{Cite journal | vauthors = McLamore WM, P'an SY, Bavley A | title = Hypnotics and Anticonvulsants. II. Halogenated Tertiary Acetylenic Carbinols | journal=Journal of Organic Chemistry | volume = 20 | pages = 109–117 | year = 1955 | doi = 10.1021/jo01119a018}}
:File:Ethchlorvynol synthesis.png{{clear left}}
The analogous compound consisting of a carbamate derived from the hydroxyl group was investigated and was shown to have a slower onset, longer duration, and increased potency, but was not developed commercially.
References
{{reflist}}
External links
- {{cite web | url = https://www.fda.gov/cder/ob/default.htm | archive-url = https://web.archive.org/web/19990428165100/http://www.fda.gov/cder/ob/default.htm | url-status = dead | archive-date = 28 April 1999 | title = Electronic Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations | publisher = Food and Drug Administration | access-date = 12 December 2005 }}
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Category:Drugs developed by AbbVie