Carbamate#Carbamate insecticides

While carbamic acids are unstable, many carbamate esters and salts are stable and well known.{{Cite journal |last1=Ghosh |first1=Arun K. |last2=Brindisi |first2=Margherita |date=2015-04-09 |title=Organic Carbamates in Drug Design and Medicinal Chemistry |journal=Journal of Medicinal Chemistry|language=en |volume=58 |issue=7 |pages=2895–2940 |doi=10.1021/jm501371s |issn=0022-2623 |pmc=4393377 |pmid=25565044}}

In water solutions, the carbamate anion slowly equilibrates with the ammonium {{chem|NH|4|+}} cation and the carbonate {{chem|CO|3|2-}} or bicarbonate {{chem|HCO|3|-}} anions:{{cite journal | last1 = Burrows | first1 = George H. | last2 = Lewis | first2 = Gilbert N. | year = 1912 | title = The equilibrium between ammonium carbonate and ammonium carbamate in aqueous solution at 25° | url = https://zenodo.org/record/2430153| journal =Journal of the American Chemical Society| volume = 34 | issue = 8| pages = 993–995 | doi = 10.1021/ja02209a003}}{{cite journal | author1 = Clark, K. G. | author2 = Gaddy, V. L. | author3 = Rist, C. E. | year = 1933 | title = Equilibria in the Ammonium Carbamate-Urea-Water System | journal =Ind. Eng. Chem.| volume = 25 | issue = 10 | pages = 1092–1096 | doi = 10.1021/ie50286a008}}{{cite journal | last1=Mani | first1=Fabrizio | last2=Peruzzini | first2=Maurizio | last3=Stoppioni | first3=Piero | title=CO2 absorption by aqueous {{chem|N|H|3}} solutions: speciation of ammonium carbamate, bicarbonate and carbonate by a {{chem|13|C}} NMR study | journal=Green Chemistry| publisher=Royal Society of Chemistry | volume=8 | issue=11 | year=2006 | issn=1463-9262 | doi=10.1039/b602051h | page=995}}

: {{chem2|H2NCO2- + 2 H2O <-> NH4+ + HCO3- + OH-}}

: {{chem2|H2NCO2- + H2O <-> NH4+ + CO3(2-)}}

Calcium carbamate is soluble in water, whereas calcium carbonate is not. Adding a calcium salt to an ammonium carbamate/carbonate solution will precipitate some calcium carbonate immediately, and then slowly precipitate more as the carbamate hydrolyzes.

The salt ammonium carbamate is generated by treatment of ammonia with carbon dioxide:{{cite book | author1 = Brooks, L. A. | author2 = Audrieta, L. F. | author3 = Bluestone, H. | author4 = Jofinsox, W. C. | title = Inorganic Syntheses | chapter = Ammonium Carbamate | year = 1946 | volume = 2 | pages = 85–86 | doi = 10.1002/9780470132333.ch23| isbn = 978-0-470-13233-3 }}

:2 NH₃ + CO₂ → NH₄[H₂NCO₂]

Carbamate esters also arise via alcoholysis of carbamoyl chlorides:

:R₂NC(O)Cl + R'OH → R₂NCO₂R' + HCl

Alternatively, carbamates can be formed from chloroformates and amines:{{cite journal | last=Chaturvedi | first=Devdutt | title=Recent Developments on the Carbamation of Amines | journal=Current Organic Chemistry| publisher=Bentham Science Publishers Ltd.| volume=15 | issue=10 | date=1 May 2011 | issn=1385-2728 | doi=10.2174/138527211795378173 | pages=1593–1624}}

:R'OC(O)Cl + R₂NH → R₂NCO₂R' + HCl

Carbamates may be formed from the Curtius rearrangement, where isocyanates formed are reacted with an alcohol.

:RCON₃ → RNCO + N₂

:RNCO + R′OH → RNHCO₂R′

Within nature carbon dioxide can bind with neutral amine groups to form a carbamate, this post-translational modification is known as carbamylation. This modification is known to occur on several important proteins; see examples below.{{Cite journal|last1=Linthwaite|first1=Victoria L.|last2=Janus|first2=Joanna M.|last3=Brown|first3=Adrian P.|last4=Wong-Pascua|first4=David|last5=O'Donoghue|first5=AnnMarie C.|last6=Porter|first6=Andrew|last7=Treumann|first7=Achim|last8=Hodgson|first8=David R. W.|last9=Cann|first9=Martin J.|date=2018-08-06|title=The identification of carbon dioxide mediated protein post-translational modifications|journal=Nature Communications|language=en|volume=9|issue=1|page=3092|doi=10.1038/s41467-018-05475-z|pmid=30082797|pmc=6078960|bibcode=2018NatCo...9.3092L|issn=2041-1723}}

The N-terminal amino groups of valine residues in the α- and β-chains of deoxyhemoglobin exist as carbamates. They help to stabilise the protein when it becomes deoxyhemoglobin, and increases the likelihood of the release of remaining oxygen molecules bound to the protein. This stabilizing effect should not be confused with the Bohr effect (an indirect effect caused by carbon dioxide).{{Cite journal|last1=Ferguson|first1=J. K. W.|last2=Roughton|first2=F. J. W.|date=1934-12-14|title=The direct chemical estimation of carbamino compounds of CO2 with hæmoglobin|journal=The Journal of Physiology|volume=83|issue=1|pages=68–86|doi=10.1113/jphysiol.1934.sp003212|issn=0022-3751|pmc=1394306|pmid=16994615}}

The ε-amino groups of the lysine residues in urease and phosphotriesterase also feature carbamate. The carbamate derived from aminoimidazole is an intermediate in the biosynthesis of inosine. Carbamoyl phosphate is generated from carboxyphosphate

rather than CO₂.{{cite journal|last1=Bartoschek|first1=S.|last2=Vorholt|first2=J. A.|last3=Thauer|first3=R. K.|last4=Geierstanger|first4=B. H.|last5=Griesinger|first5=C.|title=N-Carboxymethanofuran (carbamate) formation from methanofuran and CO₂ in methanogenic archaea: Thermodynamics and kinetics of the spontaneous reaction|journal=Eur. J. Biochem.|date=2001|volume=267|issue=11|pages=3130–3138|doi=10.1046/j.1432-1327.2000.01331.x|pmid=10824097|doi-access=free}}

Perhaps the most prevalent carbamate is the one involved in the capture of CO₂ by plants. This process is necessary for their growth. The enzyme ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO) fixes a molecule of carbon dioxide as phosphoglycerate in the Calvin cycle. At the active site of the enzyme, a Mg²⁺ ion is bound to glutamate and aspartate residues as well as a lysine carbamate. The carbamate is formed when an uncharged lysine side chain near the ion reacts with a carbon dioxide molecule from the air (not the substrate carbon dioxide molecule), which then renders it charged, and, therefore, able to bind the Mg²⁺ ion.{{Cite journal|title=Crystal Structure of the Ternary Complex of ribulose-1,5-bisphosphate Carboxylase, Mg(II), and Activator CO2 at 2.3-A Resolution|last1=T|first1=Lundqvist|last2=G|first2=Schneider|journal=Biochemistry|date=1991-01-29|volume=30|issue=4|pages=904–8|doi=10.1021/bi00218a004|language=en|pmid=1899197}}

File:RuBisCO regulation.svg

Although not usually isolated as such, the salt ammonium carbamate is produced on a large scale as an intermediate in the production of the commodity chemical urea from ammonia and carbon dioxide.

{{main|Polyurethane}}

Polyurethanes contain multiple carbamate groups as part of their structure. The "urethane" in the name "polyurethane" refers to these carbamate groups; the term "urethane links" describe how carbamates polymerize. In contrast, the substance commonly called "urethane", ethyl carbamate, is neither a component of polyurethanes, nor is it used in their manufacture. Urethanes are usually formed by reaction of an alcohol with an isocyanate. Commonly, urethanes made by a non-isocyanate route are called carbamates.{{Cn|date=January 2025}}

Polyurethane polymers have a wide range of properties and are commercially available as foams, elastomers, and solids. Typically, polyurethane polymers are made by combining diisocyanates, e.g. toluene diisocyanate, and diols, where the carbamate groups are formed by reaction of the alcohols with the isocyanates:{{Ullmann |doi=10.1002/14356007.a21_665.pub3 |title=Polyurethanes |year=2005 |last1=Adam |first1=Norbert |last2=Avar |first2=Geza |last3=Blankenheim |first3=Herbert |last4=Friederichs |first4=Wolfgang |last5=Giersig |first5=Manfred |last6=Weigand |first6=Eckehard |last7=Halfmann |first7=Michael |last8=Wittbecker |first8=Friedrich-Wilhelm |last9=Larimer |first9=Donald-Richard |last10=Maier |first10=Udo |last11=Meyer-Ahrens |first11=Sven |last12=Noble |first12=Karl-Ludwig |last13=Wussow |first13=Hans-Georg |isbn=978-3-527-30673-2 }}

:RN=C=O + R′OH → RNHC(O)OR′

File:Carbaryl-2D-skeletal.png.]]

The so-called carbamate insecticides feature the carbamate ester functional group. Included in this group are aldicarb (Temik), carbofuran (Furadan), carbaryl (Sevin), ethienocarb, fenobucarb, oxamyl, and methomyl. These insecticides kill insects by reversibly inactivating the enzyme acetylcholinesterase (AChE inhibition){{cite journal |pmc=1567830|year=1990|last1=Fukuto|first1=T. R.|title=Mechanism of action of organophosphorus and carbamate insecticides|journal=Environmental Health Perspectives |volume=87|pages=245–254|doi=10.1289/ehp.9087245|pmid=2176588}} (IRAC mode of action 1a). The organophosphate pesticides also inhibit this enzyme, although irreversibly, and cause a more severe form of cholinergic poisoning{{Ullmann|first=Robert L.|last=Metcalf|title=Insect Control|doi=10.1002/14356007.a14_263}} (the similar IRAC MoA 1b).

Fenoxycarb has a carbamate group but acts as a juvenile hormone mimic, rather than inactivating acetylcholinesterase.{{cite web|url=http://pmep.cce.cornell.edu/profiles/extoxnet/dienochlor-glyphosate/fenoxycarb-ext.html|publisher=Cornell University|title=Pesticide Information Project: Fenoxycarb|access-date=15 June 2019}}

The insect repellent icaridin is a substituted carbamate.{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/Icaridin|title=PubChem Compound Summary for CID 125098, Icaridin|author=((National Center for Biotechnology Information))|website=Pubchem|access-date=2024-01-08}}

Besides their common use as arthropodocides/insecticides, they are also nematicidal. One such is Oxamyl.

Sales have declined dramatically over recent decades.{{cite journal|year=2020|publisher=Elsevier|last1=Sparks|first1=Thomas|last2=Crossthwaite|first2=Andrew|last3=Nauen|first3=Ralf|last4=Banba|first4=Shinichi|last5=Cordova|first5=Daniel|last6=Earley|first6=Fergus|last7=Ebbinghaus-Kintscher|first7=Ulrich|last8=Fujioka|first8=Shinsuke|last9=Hirao|first9=Ayako|last10=Karmon|first10=Danny|last11=Kennedy|first11=Robert|last12=Nakao|first12=Toshifumi|last13=Popham|first13=Holly|last14=Salgado|first14=Vincent|last15=Watson|first15=Gerald|last16=Wedel|first16=Barbara|last17=Wessels|first17=Frank|volume=167|page=104587|journal=Pesticide Biochemistry and Physiology|issn=0048-3575|doi=10.1016/j.pestbp.2020.104587|title=Insecticides, biologics and nematicides: Updates to IRAC's mode of action classification - a tool for resistance management|pmid=32527435 |doi-access=free|bibcode=2020PBioP.16704587S }}

Among insecticide resistance mutations in esterases, carbamate resistance most commonly involves acetylcholinesterase (AChE) desensitization, while organophosphate resistance most commonly is carboxylesterase metabolization.{{cite journal|year=2005|publisher=Elsevier BV|last1=Oakeshott|first1=John|last2=Devonshire|first2=Alan|last3=Claudianos|first3=Charles|last4=Sutherland|first4=Tara|last5=Horne|first5=Irene|last6=Campbell|first6=Peter|last7=Ollis|first7=David|last8=Russell|first8=Robyn|pages=269–275|volume=157-158|journal=Chemico-Biological Interactions|issn=0009-2797|s2cid=32597626|pmid=16289012|doi=10.1016/j.cbi.2005.10.041|title=Comparing the organophosphorus and carbamate insecticide resistance mutations in cholin- and carboxyl-esterases|bibcode=2005CBI...157..269O }}

While the carbamate acetylcholinesterase inhibitors are commonly referred to as "carbamate insecticides" due to their generally high selectivity for insect acetylcholinesterase enzymes over the mammalian versions, the most potent compounds such as aldicarb and carbofuran are still capable of inhibiting mammalian acetylcholinesterase enzymes at low enough concentrations that they pose a significant risk of poisoning to humans, especially when used in large amounts for agricultural applications. Other carbamate based acetylcholinesterase inhibitors are known with even higher toxicity to humans, and some such as T-1123 and EA-3990 were investigated for potential military use as nerve agents. However, since all compounds of this type have a quaternary ammonium group with a permanent positive charge, they have poor blood–brain barrier penetration, and also are only stable as crystalline salts or aqueous solutions, and so were not considered to have suitable properties for weaponisation.{{cite book | url=https://books.google.com/books?id=MXKDBAAAQBAJ&pg=PA338 | title=Handbook of Toxicology of Chemical Warfare Agents | publisher=Academic Press | editor=Gupta, Ramesh C | year=2015 | location=Cambridge, Massachusetts, United States | pages=338–339 | isbn=978-0-12-800494-4}}{{cite book | last=Ellison | first=D | title=Handbook of chemical and biological warfare agents | publisher=CRC Press | publication-place=Boca Raton | year=2008 | isbn=978-0-8493-1434-6 | oclc=82473582 }}

Iodopropynyl butylcarbamate is a wood and paint preservative and used in cosmetics.{{cite journal|last=Badreshia|first=S.|year=2002|title=Iodopropynyl butylcarbamate|journal=Am. J. Contact Dermat.|volume=13|issue=2|pages=77–79|issn=1046-199X|doi=10.1053/ajcd.2002.30728|pmid=12022126}}

Some of the most common amine protecting groups, such as Boc,{{cite book | doi = 10.1002/9783527631827.ch1 | chapter = Protection Reactions | editor = Andrew B. Hughes | author1 = Vommina V. Sureshbabu | author2 = Narasimhamurthy Narendra | volume = 4 | series = Amino Acids, Peptides and Proteins in Organic Chemistry | title = Protection Reactions, Medicinal Chemistry, Combinatorial Synthesis | publisher = Wiley-VCH | chapter-url = https://books.google.com/books?id=uZK2i-FkeAUC&pg=PP18 | isbn = 9783527641574 | pages = XVIII – LXXXIV| year = 2011 }} Fmoc,{{cite book |doi=10.1016/s0076-6879(97)89043-x |chapter=[4] Standard Fmoc protocols |title=Solid-Phase Peptide Synthesis |series=Methods in Enzymology |date=1997 |last1=Wellings |first1=Donald A. |last2=Atherton |first2=Eric |volume=289 |pages=44–67 |pmid=9353717 |isbn=9780121821906 }} benzyl chloroformate{{Cite book|url=https://org.chem.uoa.gr/istoriki_exelixi_toy_ergastirioy_organikis_chimeias_historical_development_of_organic_chemistry_laboratory/afieroma_ston_leonida_zerba_dedication_to_prof_leonidas_zervas/i_symboli_toy_l_zerba_stin_epistimi_tis_chimeias_contribution_of_l_zervas_in_the_science_of_chemistry/|title=The Chemistry of Polypeptides|publisher=Plenum Press|year=1973|isbn=978-1-4613-4571-8|editor-last=Katsoyannis|editor-first=P. G.|location=New York|doi=10.1007/978-1-4613-4571-8|s2cid=35144893|access-date=2021-04-01|archive-date=2022-10-13|archive-url=https://web.archive.org/web/20221013010830/https://org.chem.uoa.gr/istoriki_exelixi_toy_ergastirioy_organikis_chimeias_historical_development_of_organic_chemistry_laboratory/afieroma_ston_leonida_zerba_dedication_to_prof_leonidas_zervas/i_symboli_toy_l_zerba_stin_epistimi_tis_chimeias_contribution_of_l_zervas_in_the_science_of_chemistry/|url-status=dead}} and trichloroethyl chloroformate{{Cite journal|last1=Marullo|first1=N. P.|last2=Wagener|first2=E. H.|date=1969-01-01|title=Structural organic chemistry by nmr. III. Isomerization of compounds containing the carbon-nitrogen double bond|journal=Tetrahedron Letters|volume=10|issue=30|pages=2555–2558|doi=10.1016/S0040-4039(01)88566-X}} are carbamates.

Urethane (ethyl carbamate) was once produced commercially in the United States as a chemotherapy agent and for other medicinal purposes. It was found to be toxic and largely ineffective.{{cite journal |pmid= 5933438 |last1= Holland |first1= J. R. |last2= Hosley |first2= H. |last3= Scharlau |first3= C. |last4= Carbone |first4= P. P. |last5= Frei |first5= E. III |last6= Brindley |first6= C. O. |last7= Hall |first7= T. C. |last8= Shnider |first8= B. I. |last9= Gold |first9= G. L. |last10= Lasagna |first10= L. |last11= Owens |first11= A. H. Jr |last12= Miller |first12= S. P. |title= A controlled trial of urethane treatment in multiple myeloma |journal=Blood|volume= 27 |issue= 3 |pages= 328–42 |date= 1 March 1966 |doi= 10.1182/blood.V27.3.328.328 |issn= 0006-4971 |doi-access= free }} It is occasionally used in veterinary medicine in combination with other drugs to produce anesthesia.{{cite web|publisher=Virginia Commonwealth University |author=((The Chemical/Biological Safety Section (CBSS) of the Office of Environmental Health and Safety)) |url=http://www.vcu.edu/oehs/chemical/biosafe/urethane.pdf|title= Working with Urethane |archive-url=https://web.archive.org/web/20130511205145/http://www.vcu.edu/oehs/chemical/biosafe/urethane.pdf |archive-date=2013-05-11 }}

Some carbamate derivatives are used in human pharmacotherapy:

• The acetylcholinesterase inhibitor chemical class includes neostigmine and rivastigmine, both of which have a chemical structure based on the natural alkaloid physostigmine.

• The tranquilizer, sedative-hypnotic, and muscle relaxant, meprobamate (branded Miltown) was commonly prescribed from the 1950s through the 1970s. It became a familiar and popular prescription drug, approved for medical use in the U.S. by the Food and Drug Administration and indicated to treat a variety of neurological symptoms and movement disorders (e.g. motor/physical and vocal/phonic tics caused by Tourette's Syndrome; the drug also exhibited anticonvulsant effects and was able to reduce the frequency of seizures and even stop a seizure in place, including seizures due to Delirium Tremens in alcohol withdrawal, or abrupt barbiturate withdrawal. Finally, meprobamate worked an anxiolytic and muscle relaxant, indicated for alleviating generalized anxiety, social anxiety, panic attack or acute panic attack, obsessive-compulsive disorder (OCD) and associated anxieties (e.g. obsessive phobia) or compulsive anxiety such as easing the internal tensione that comes forcibly repressing the compulsion to "tic" (i.e make a certain or movement) or the compulsion to rid yourself of nearly all possessions and maintaining inventory of items remaining) based upon the false belief that decluttering material possessions will "declutter" or simplify one's life. Finally, as a muscle relaxant and/or [[antispasmodic (depending on one's dose, tolerance, use frequency, metabolism, etc.) meprobamate could lessen muscular tension and even the desire to feel, care about, or respond to, said tension. A starting dose was typically orally ingesting one 300 mg Miltown (meprobamate) tablet as needed, up to 3 or even 4 times daily. Habituation and tolerance were quickly attained, hence doses in the range of 900 - 1,600mg over the course of a day is comfortably within the drug's therapeutic index. Barbiturates, to the contrary, had relatively narrow therapeutic windows, such that a patient was risking fatal overdoseif a patient took 1-2 extra pills, they risked lethal respiratory failure. The quick-acting and quick-onset barbiturates were particularly lethal, such as pentobarbital (Nembutal) and secobarbital (Seconal), but even the intermediate-acting barbiturates such as amobarbital (Amytal) and butabarbital (Butasol) present considerable risk relative to their successors, e.g. benzodiazepines, Placidyl, Doriden, and Noludar. Meprobamate was advertised on and its derivatives like carisoprodol, felbamate, mebutamate, phenprobamate, and tybamate, a class of anxiolytic and muscle relaxant drugs widely used in the 1960s before the rise of benzodiazepines, and still used nowadays in some cases. Carbachol is primarily used for various ophthalmic purposes.Carbachol {{Drugs.com|MTM|carbachol}}. Accessed 27 April 2021.

• Soma (carisoprodol) is a CNS depressant and a prodrug of meprobamate; initially acting primarily as a mildy-sedating muscle relaxant and muscle pain reliever; after 2-3 hours, 20-30% of initial dose converts into active metabolite meprobamate, synergistically working together to potentiate, or add on to/increase, the existing sedation and muscle relaxation and analgesia. As the body starts to metabolize more carisoprodol into meprobamate (reducing the total amount of carisoprodol in the body, and boosting the amount of meprobamate, to get somewhere close to "equalized" or 1:1 proportion. By the time the substances are at roughly equal proportion after 5-6 hours, muscle relaxation turns into muscle weakness; pain relief turns into numbness; the tranquilizing, heavier sedative and hypnotic effect of meprobamate start to overpower the initial effects of the Soma

• Valmid or Valamin was a carbamate derivative chemically named ethinamate. It was withdrawn from the market in the U.S. and Netherlands around 1990. It was a potent sleeping pill (that is, a hypnotic or soporific agent_ with a rapid-onset of action to get the user to sleep, albeit with a short duration of action, so it was only goof for falling asleep, but would do little to nothing to ]] keep you asleep. Relative to contemporary sleeping pills, such as the z-drugs, ethinamate shares most similarity to zaleplon (Sonata globally; ZapSign10 and Hyplon elsewhere, with a quick onset time, an extremely brief half-life, and it is for inducing sleep. For short-temrm insomnia treatment, tolerance develops within just a week. Valmid was the substance that Elvis Presley took eight tablets before going to sleep on the night of August 15th-16th, 1977. Having taken Valmind for sleep for well over the recommend 1-2 weeks, it's difficult to believe that even eight tablets could have sufficiently put him to sleep.https://pubchem.ncbi.nlm.nih.gov/compound/Ethinamate NIH molecular analysis report

• The protease inhibitor darunavir for HIV treatment also contains a carbamate functional group.{{DrugBank|DB01264}}. Accessed 27 April 2021.

• Ephedroxane, an aminorex analogue used as a stimulant, also falls into the carbamate category.{{cite journal | vauthors = Hikino H, Ogata K, Kasahara Y, Konno C | title = Pharmacology of ephedroxanes | journal = Journal of Ethnopharmacology | volume = 13 | issue = 2 | pages = 175–191 | date = May 1985 | doi = 10.1016/0378-8741(85)90005-4 | pmid = 4021515 }}

{{Main|Carbamate poisoning}}

Besides inhibiting human acetylcholinesterase{{cite journal | pmc=3648782 | pmid=24179466 | doi=10.2174/1570159X11311030006 | volume=11 | title=Acetylcholinesterase inhibitors: pharmacology and toxicology | year=2013 | journal=Curr Neuropharmacol| pages=315–35 | last1 = Colović | first1 = MB | last2 = Krstić | first2 = DZ | last3 = Lazarević-Pašti | first3 = TD | last4 = Bondžić | first4 = AM | last5 = Vasić | first5 = VM| issue=3 }} (although to a lesser degree than the insect enzyme), carbamate insecticides also target human melatonin receptors.{{cite journal | pmc=5318275 | pmid=28027439 | doi=10.1021/acs.chemrestox.6b00301 | volume=30 | title=Carbamate Insecticides Target Human Melatonin Receptors | year=2017 | journal=Chem Res Toxicol| pages=574–582 | last1 = Popovska-Gorevski | first1 = M | last2 = Dubocovich | first2 = ML | last3 = Rajnarayanan | first3 = RV| issue=2 }} The human health effects of carbamates are well documented in the list of known endocrine disruptor compounds.{{Cite journal |last1=Marais |first1=Simone |last2=Diase |first2=Elsa |last3=Pereira |first3=Maria de Lourdes |date=2012 |title=Carbamates: Human Exposure and Health Effects |url=https://www.researchgate.net/publication/232936639 |journal=The Impact of Pesticides|volume=21 |page=38 |via=Research Gate}} Clinical effects of carbamate exposure can vary from slightly toxic to highly toxic depending on a variety of factors including such as dose and route of exposure with ingestion and inhalation resulting in the most rapid clinical effects. These clinical manifestations of carbamate intoxication are muscarinic signs, nicotinic signs, and in rare cases central nervous system signs.

There are two oxygen atoms in a carbamate (1), ROC(=O)NR₂, and either or both of them can be conceptually replaced by sulfur. Analogues of carbamates with only one of the oxygens replaced by sulfur are called thiocarbamates (2 and 3). Carbamates with both oxygens replaced by sulfur are called dithiocarbamates (4), RSC(=S)NR₂.{{cite encyclopedia|title=Dithiocarbamic Acid and Derivatives|encyclopedia=Ullmann's Encyclopedia of Industrial Chemistry|author=Rüdiger Schubart|year=2000|doi=10.1002/14356007.a09_001|publisher=Wiley-VCH|isbn=3-527-30673-0|place=Weinheim}}

There are two different structurally isomeric types of thiocarbamate:

• O-thiocarbamates (2), ROC(=S)NR₂, where the carbonyl group (C=O) is replaced with a thiocarbonyl group (C=S){{cite journal |last1=Walter |first1=W. |last2=Bode |first2=K.-D. |title=Syntheses of Thiocarbamates |journal=Angewandte Chemie International Edition in English |date=April 1967 |volume=6 |issue=4 |pages=281–293 |doi=10.1002/anie.196702811}}
• S-thiocarbamates (3), RSC(=O)NR₂, where the R–O– group is replaced with an R–S– group

O-thiocarbamates can isomerise to S-thiocarbamates, for example in the Newman–Kwart rearrangement.{{cite journal |title=Thiophenols from Phenols: 2-Naphthalenethiol |last1=Newman |first1=Melvin S. |last2=Hetzel |first2=Frederick W. |journal=Org. Synth. |year=1971 |volume=51 |page=139 |doi=10.15227/orgsyn.051.0139}}

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The etymology of the words "urethane" and "carbamate" are highly similar but not the same. The word "urethane" was first coined in 1833 by French chemist Jean-Baptiste Dumas.{{Cite book |title=A dictionary of chemistry |date=2008 |publisher=Oxford University Press |others=John Daintith |isbn=978-1-61583-965-0 |edition=6th |location=New York |oclc=713875281}}{{Cite journal |last=Dumas |first=Jean |date=1833 |title=Recherches de chimie organique |url=https://books.google.com/books?id=xEFRnP2_OmQC&q=j.+Dumas%2C+%27Recherches+de+chimie+organique%27&pg=PA499 |journal=Annales de Chimie et de Physique|series=2nd series |volume=56 |pages=496–556}} Dumas states "Urethane. The new ether, brought into contact with liquid and concentrated ammonia, exerts on this substance a reaction so strong that the mixture boils, and sometimes even produces a sort of explosion. If the ammonia is in excess, all the ether disappears. It forms ammonium hydrochlorate and a new substance endowed with interesting properties." Dumas appears to be naming this compound urethane. However, later Dumas states "While waiting for opinion to settle on the nature of this body, I propose to designate by the names of urethane and oxamethane the two materials which I have just studied, and which I regard as types of a new family, among nitrogenous substances. These names which, in my eyes, do not prejudge anything in the question of alcohol and ethers, will at least have the advantage of satisfying chemists who still refuse to accept our theory." The word urethane is derived from the words "urea" and "ether" with the suffix "-ane" as a generic chemical suffix, making it specific for the R2NC(=O)OR' (R' not = H) bonding structure.{{Cite web |title=urethane {{!}} Etymology, origin and meaning of urethane by etymonline |url=https://www.etymonline.com/word/urethane |access-date=2023-03-29 |website=www.etymonline.com |language=en}}

The use of the word "carbamate" appears to come later only being traced back to at least 1849, in a description of Dumas's work by Henry Medlock.{{Cite journal |last=Medlock |first=Henry |date=1849 |title=XXIX.—Researches on the amyl series |journal=Q. J. Chem. Soc.|volume=1 |issue=4 |pages=368–379 |doi=10.1039/qj8490100368 |issn=1743-6893|url=https://zenodo.org/record/2080479 }} Medlock states "It is well known that the action of ammonia on chloro-carbonate (phosgene) of ethyl gives rise to the formation of the substance which Dumas, the discoverer, called urethane, and which we are now in the habit of considering as the ether of carbamic acid." This suggests that instead of continuing with the urethane family naming convention Dumas coined, they altered the naming convention to ethyl ether of carbamic acid. Carbamate is derived from the words "carbamide", otherwise known as urea, and "-ate" a suffix which indicates the salt or ester of an acid.{{Cite web |title=Definition of CARBAMATE |url=https://www.merriam-webster.com/dictionary/carbamate |access-date=2023-03-29 |website=www.merriam-webster.com |language=en}}{{Cite journal |last=Divers |first=Edward |date=1870-01-01 |title=XXVII.—On the precipitation of solutions of ammonium carbonate, sodium carbonate, and ammonium carbamate by calcium chloride |url=https://pubs.rsc.org/en/content/articlelanding/1870/js/js8702300359 |journal=Journal of the Chemical Society|language=en |volume=23 |pages=359–364 |doi=10.1039/JS8702300359 |issn=0368-1769}}

Both words have roots deriving from urea. Carbamate is less-specific because the -ate suffix is ambiguous for either the salt or ester of a carbamic acid. However, the -ate suffix is also more specific because it suggests carbamates must be derived from the acid of carbamate, or carbamic acids. Although, a urethane has the same chemical structure as a carbamate ester moiety, a urethane not derived from a carbamic acid is not a carbamate ester. In other words, any synthesis of the R2NC(=O)OR' (R' not = H) moiety that does not derive from carbamic acids is not a carbamate ester but instead a urethane. Furthermore, carbamate esters are urethanes but not all urethanes are carbamate esters. This further suggests that polyurethanes are not simply polycarbamate-esters because polyurethanes are not typically synthesized using carbamic acids.

IUPAC states "The esters are often called urethanes or urethans, a usage that is strictly correct only for the ethyl esters."{{Cite book |chapter=Carbamates (C00803) |title=Goldbook |url=https://goldbook.iupac.org/terms/view/C00803 |access-date=2023-03-29 |publisher=IUPAC|doi=10.1351/goldbook.C00803 }} But also states, "An alternative term for the compounds R2NC(=O)OR' (R' not = H), esters of carbamic acids, R,NC(=O)OH, in strict use limited to the ethyl esters, but widely used in the general sense".{{Cite journal |last1=Moss |first1=G. P. |last2=Smith |first2=P. a. S. |last3=Tavernier |first3=D. |date=1995-01-01 |title=Glossary of class names of organic compounds and reactivity intermediates based on structure (IUPAC Recommendations 1995) |journal=Pure and Applied Chemistry|language=de |volume=67 |issue=8–9 |pages=1307–1375 |doi=10.1351/pac199567081307 |s2cid=95004254 |issn=1365-3075|doi-access=free }} IUPAC provides these statements without citation.

• Methyl carbamate
• Ethyl carbamate
• Polyurethane
• Cholinesterase inhibitor

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{{cite web|url=http://irac-online.org/documents/moa-classification/|title=IRAC Mode of Action Classification Scheme Version 9.4|publisher=Insecticide Resistance Action Committee|type=pdf|date=March 2020}}

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