Opioid antagonist - wikipedia Opioid antagonist An opioid antagonist, or opioid receptor antagonist, is a receptor antagonist that acts on one or more of the opioid receptors. Naloxone and naltrexone are commonly used opioid antagonist drugs which are competitive antagonists that bind to the opioid receptors with higher affinity than agonists but do not activate the receptors. This effectively blocks the receptor, preventing the body from responding to opioids and endorphins. Some opioid antagonists are not pure antagonists but in fact do produce some weak opioid partial agonist effects, and can produce analgesic effects when administered in high doses to opioid - naive individuals. Examples of such compounds include nalorphine and levallorphan. However, the analgesic effects from these specific drugs are limited and tend to be accompanied by dysphoria, most likely due to additional agonist action at the κ - opioid receptor. As they induce opioid withdrawal effects in people who are taking, or have recently used, opioid full agonists, these drugs are generally considered to be antagonists for practical purposes. The weak partial agonist effect can be useful for some purposes, and has previously been used for purposes such as long - term maintenance of former opioid addicts using nalorphine, however it can also have disadvantages such as worsening respiratory depression in patients who have overdosed on non-opioid sedatives such as alcohol or barbiturates. Naloxone on the other hand has no partial agonist effects, and is in fact a partial inverse agonist at μ - opioid receptors, and so is the preferred antidote drug for treating opioid overdose. Naltrexone is also a partial inverse agonist, and this property is exploited in treatment of opioid addiction, as a sustained course of low - dose naltrexone can reverse the altered homeostasis which results from long - term abuse of opioid agonist drugs. This is the only treatment available which can reverse the long - term after effects of opioid addiction known as post acute withdrawal syndrome, which otherwise tends to produce symptoms such as depression and anxiety that may lead to eventual relapse. A course of low - dose naltrexone is thus often used as the final step in the treatment of opioid addiction after the patient has been weaned off the substitute agonist such as methadone or buprenorphine, in order to restore homeostasis and minimize the risk of post acute withdrawal syndrome once the maintenance agonist has been withdrawn. Contents 1 List of opioid antagonists 1.1 Centrally active 1.1. 1 Marketed 1.1. 2 Discontinued or rarely used 1.1. 3 Under development 1.1. 4 Never marketed 1.2 Peripherally restricted 1.2. 1 Marketed 1.2. 2 Under development currently or previously 1.3 Miscellaneous 2 Selective antagonists 3 Depersonalization disorder 4 In popular culture 5 References 6 External links List of opioid antagonists The following are all μ - opioid receptor ( MOR ) antagonists or inverse agonists. Many of them also bind to the κ - opioid receptor ( KOR ) and / or δ - opioid receptor ( DOR ), where they variously behave as antagonists and / or agonists. Centrally active These drugs are used mainly as antidotes to reverse opioid overdose and in the treatment of alcohol dependence and opioid dependence ( by blocking the effects, namely euphoria, of opioids so as to discourage abuse ). Marketed Naloxone Naltrexone Nalmefene Diprenorphine is used in veterinary medicine only. Discontinued or rarely used Nalorphine Nalorphine dinicotinate Levallorphan Under development Samidorphan Never marketed Nalodeine Peripherally restricted These drugs are used mainly in the treatment of opioid - induced constipation. Marketed Alvimopan Methylnaltrexone Naloxegol Under development currently or previously 6β - Naltrexol Axelopran Bevenopran Methylsamidorphan Naldemedine Miscellaneous Buprenorphine and dezocine are partial agonists of the MOR but antagonists of the KOR. Contrarily, eptazocine is an antagonist of the MOR but an agonist of the KOR ; the same is also true for nalorphine and levallorphan. A variety of partial agonists or mixed agonists - antagonists of the MOR and KOR are also marketed, and include butorphanol, levorphanol, nalbuphine, pentazocine, and phenazocine. All of the aforementioned drugs may be described as opioid modulators instead of as pure antagonists. With the sole exception of nalorphine, all of the preceding are used as analgesics ( by virtue of the fact that both MOR and KOR agonism independently confer pain relief ). However, these opioid analgesics have atypical properties in comparison to the prototypical pure MOR full agonist opioid analgesics, such as less or no risk of respiratory depression for MOR partial agonists and antagonists, reduced or no euphoria, abuse potential, and dependence liability with MOR partial agonists / antagonists, and use - and dose - limiting side effects such as dysphoria and hallucinations with KOR agonists. In addition, by virtue of its KOR antagonism, buprenorphine ( as buprenorphine / samidorphan ( ALKS - 5461 ) or buprenorphine / naltrexone to block its MOR agonism ) is under investigation for the treatment of depression and cocaine dependence, as are other KOR antagonists such as CERC - 501 ( LY - 2456302 ) and, previously, JDTic and PF - 4455242 ( both discontinued due to toxicity concerns ). Selective antagonists All of the centrally active opioid antagonists used widely in medicine are non-selective, either blocking multiple opioid receptors, or blocking the MOR but activating the KOR. However, for scientific research, selective antagonists are needed which can block one of the opioid receptors but without affecting the others. This has led to the development of antagonists which are highly selective to one of the four receptors : Cyprodime is a selective MOR antagonist Naltrindole is a selective DOR antagonist Norbinaltorphimine is a selective KOR antagonist J - 113,397 is a selective nociceptin receptor ( NOP ) antagonist Other selective antagonists are also known, but the four listed above were the first selective antagonists discovered for each respective opioid receptor, and are still the most widely used. In addition to selective antagonists, AT - 076 is a non-selective, balanced antagonist of all four of the opioid receptors, and was the first such agent to be discovered. Depersonalization disorder Naloxone and naltrexone have both been studied in the treatment of depersonalization disorder. In a 2001 study with naloxone, three of fourteen patients lost their depersonalization symptoms entirely, and seven showed marked improvement. The findings of a 2005 naltrexone study were slightly less promising, with an average of a 30 % reduction of symptoms, as measured by three validated dissociation scales. The more dramatic result of naloxone versus naltrexone is suspected to be due to different opioid receptor affinity / selectivity with naloxone ( specifically, more potent KOR blockade ), which appears to be better suited to individuals suffering from depersonalization disorder. In popular culture In the episode of House, `` Skin Deep '', opioid antagonist drugs were administered in order to completely remove the patient 's heroin induced addiction / withdrawal symptoms ( during an induced coma in order to relieve the extreme pain of their use ), so that an accurate diagnosis of paraneoplastic syndrome caused by cancer was differentiated. In an episode of Royal Pains, a character dangerously tries to undergo a procedure ( and go under anaesthesia ) in his own home. In an episode of Hannibal, Dr. Lecter administers Naloxone to Jack Crawford 's wife after she tries to commit suicide by overdosing on morphine. References Jump up ^ Kawamoto H, Ozaki S, Itoh Y, Miyaji M, Arai S, Nakashima H, Kato T, Ohta H, Iwasawa Y ( 1999 ). `` Discovery of the first potent and selective small molecule opioid receptor - like ( ORL1 ) antagonist : 1 - ( ( 3R, 4R ) - 1 - cyclooctylmethyl - 3 - hydroxymethyl - 4 - piperidyl ) - 3 - ethyl - 1, 3 - dihydro - 2H - benzimidazol - 2 - one ( J - 113397 ) ''. J. Med. Chem. 42 ( 25 ) : 5061 -- 3. PMID 10602690. doi : 10.1021 / jm990517p. Jump up ^ Zaveri NT, Journigan VB, Polgar WE ( 2015 ). `` Discovery of the first small - molecule opioid pan antagonist with nanomolar affinity at mu, delta, kappa, and nociceptin opioid receptors ''. ACS Chem Neurosci. 6 ( 4 ) : 646 -- 57. PMC 4401318. PMID 25635572. doi : 10.1021 / cn500367b. Jump up ^ Nuller, Yuri. `` Effect of naloxone therapy on depersonalization : a pilot stud ''. Sage. Retrieved 10 / 8 / 2011. Check date values in : access - date = ( help ) Jump up ^ Simeon, Daphne. `` An Open Trial of Naltrexone in the Treatment of Depersonalization Disorder ''. Journal of Clinical Psychopharmacology. Retrieved 2011 - 10 - 13. External links David S, Lancaster T, Stead LF. Opioid antagonists for smoking cessation ( Cochrane Review ), The Cochrane Library, Issue 2, 2005. Chichester, UK : John Wiley & Sons, Ltd. Opioid Antagonists at the US National Library of Medicine Medical Subject Headings ( MeSH ) Antidotes ( V03AB ) Nervous system Nerve agent / Organophosphate poisoning Atropine Biperiden Diazepam Oximes Obidoxime Pralidoxime see also : Cholinesterase Barbiturate overdose Bemegride Ethamivan Benzodiazepine overdose Cyprodenate Flumazenil GHB overdose Physostigmine SCH - 50911 Opioid overdose Diprenorphine Doxapram Nalmefene Nalorphine Naloxone Naltrexone Reversal of neuromuscular blockade Sugammadex Circulatory system Beta blocker Glucagon Digoxin toxicity Digoxin Immune Fab Heparin Protamine Other Arsenic poisoning Dimercaprol Succimer Cyanide poisoning 4 - Dimethylaminophenol Hydroxocobalamin nitrite Amyl nitrite Sodium nitrite Sodium thiosulfate Hydrofluoric acid Calcium gluconate Methanol / Ethylene glycol poisoning Primary alcohols : Ethanol Fomepizole Paracetamol toxicity ( Acetaminophen ) Acetylcysteine Glutathione Methionine Toxic metals ( cadmium lead mercury thallium ) Dimercaprol Edetates Prussian blue Other iodine - 131 Potassium iodide Methylthioninium chloride oxidizing agent Potassium permanganate Prednisolone / promethazine Emetic Copper sulfate Ipecacuanha Syrup of ipecac WHO - EM Withdrawn from market Clinical trials : Phase III Never to phase III Treatment of drug dependence ( N07B ) Nicotine dependence Bupropion Cytisine Lobeline Mecamylamine Varenicline AA ( Clonidine ) Alcohol dependence AD inhibitor ( Disulfiram Calcium carbimide Hydrogen cyanamide ) Acamprosate Opioid antagonists ( Naltrexone Nalmefene ) Topiramate AA ( Clonidine ) Baclofen Metadoxine Phenibut Opioid dependence AA ( Clonidine Lofexidine ) Ibogaine Opioids Buprenorphine ( + naloxone ) Levacetylmethadol Methadone Dihydrocodeine Dihydroetorphine Hydromorphone ( extended - release ) Morphine ( extended - release ) Opioid antagonists ( Naltrexone Nalmefene ) Benzodiazepine dependence AA ( Clonidine ) Benzodiazepines ( Diazepam Lorazepam Chlordiazepoxide Oxazepam ) Barbiturates ( Phenobarbital ) Opioid receptor modulators MOR Agonists ( abridged ; see here for a full list ) : 3 - HO - PCP 7 - Acetoxymitragynine 7 - Hydroxymitragynine ψ - Akuammigine α - Chlornaltrexamine α - Narcotine Acetyldihydrocodeine Acetylfentanyl Acrylfentanyl Adrenorphin ( metorphamide ) AH - 7921 Akuammicine Akuammidine Alfentanil Anileridine Apparicine β - Endorphin BAM - 12P BAM - 18P BAM - 22P Benzhydrocodone Benzylmorphine Bezitramide Biphalin BU08070 Buprenorphine Butorphan Butorphanol Butyrfentanyl BW - 373U86 Carfentanil Casokefamide Cebranopadol Chloroxymorphamine Codeine DADLE DAMGO ( DAGO ) Dermorphin Desmetramadol ( desmethyltramadol ) Desomorphine Dextromoramide Dextropropoxyphene ( propoxyphene ) Dezocine Dimenoxadol Dimethylaminopivalophenone Eluxadoline Diamorphine ( heroin ) Dihydrocodeine Dihydroetorphine Dihydromorphine Diphenoxylate Dipipanone Dynorphin A Embutramide Endomorphin - 1 Endomorphin - 2 Eseroline Ethylmorphine Etorphine Fentanyl Fluorophen Frakefamide Furanylfentanyl Hemorphin - 4 Herkinorin Hodgkinsine Hydrocodone Hydromorphinol Hydromorphone IBNtxA Ketamine Ketobemidone Kratom Laudanosine Lefetamine Leu - enkephalin Levacetylmethadol Levomethorphan Levorphanol Lexanopadol Loperamide Loxicodegol Matrine Meptazinol Met - enkephalin ( metenkefalin ) Methadone Metkefamide Metopon Mitragynine Mitragynine pseudoindoxyl Morphiceptin Morphine Nalbuphine Nalbuphine sebacate NalBzOH Nalmexone Naltalimide Neopine NFEPP Nicocodeine Nicodicodeine Nicomorphine NKTR - 181 Norketamine Octreotide Oliceridine OM - 3 - MNZ Oripavine Oxycodone Oxymorphazone Oxymorphonazine Oxymorphone Oxymorphone phenylhydrazone OxyPNPH Papaver somniferum ( opium ) Pentazocine Pericine Pethidine ( meperidine ) Phenazocine Phencyclidine Piminodine Piritramide PL - 017 Prodine Propiram PZM21 Racemethorphan Racemorphan Remifentanil Salsolinol SC - 17599 Sinomenine Sufentanil Tapentadol Tetrahydropapaveroline TH - 030418 Thebaine Thienorphine Tianeptine Tilidine Tramadol Trimebutine TRIMU 5 TRV734 Tubotaiwine U-47700 Valorphin Viminol Xorphanol PAMs : BMS - 986121 BMS - 986122 Antagonists : ( 3S, 4S ) - Picenadol 2 - ( S ) - N, N - ( R ) - Viminol 3CS - nalmefene 4 - Caffeoyl - 1, 5 - quinide 4 ′ - Hydroxyflavanone 4 ', 7 - Dihydroxyflavone 6β - Naltrexol 6β - Naltrexol - d4 18 - MC α - Gliadin β - Chlornaltrexamine β - Funaltrexamine Akuammine Alvimopan AM - 251 Apigenin AT - 076 Axelopran Bevenopran Catechin Catechin gallate Clocinnamox CTAP CTOP Cyclofoxy Cyprodime Diacetylnalorphine Diprenorphine ECG EGC Epicatechin Eptazocine Gemazocine Ginsenoside R Hyperoside Ibogaine Levallorphan Lobeline LY - 255582 LY - 2196044 Methocinnamox Methylnaltrexone Methylsamidorphan chloride Naldemedine Nalmefene Nalodeine ( N - allylnorcodeine ) Nalorphine Nalorphine dinicotinate Naloxazone Naloxegol Naloxol Naloxonazine Naloxone Naltrexazone Naltrexonazine Naltrexone Naltrindole Naringenin Noribogaine Oxilorphan Pawhuskin A Rimonabant Quadazocine Samidorphan Taxifolin Unknown / unsorted : Cannabidiol Coronaridine Cyproterone acetate Dihydroakuuamine Tabernanthine Tetrahydrocannabinol DOR Agonists : 3CS - nalmefene 6 ' - GNTI 7 - SIOM ADL - 5747 ( PF - 04856881 ) ADL - 5859 Alazocine ( SKF - 10047 ) Amoxapine AR - M100390 ( ARM390 ) AZD2327 β - Endorphin BAM - 18P Biphalin BU - 48 Butorphan Butorphanol BW - 373U86 Casokefamide Cebranopadol Codeine Cyclazocine DADLE Deltorphin A Deltorphin I Deltorphin II Desmethylclozapine Desmetramadol ( desmethyltramadol ) Dezocine Diamorphine ( heroin ) Dihydroetorphine Dihydromorphine DPDPE DPI - 221 DPI - 3290 DSLET Ethylketazocine Etorphine Fentanyl FIT Fluorophen Hemorphin - 4 Hydrocodone Hydromorphone Ibogaine Isomethadone JNJ - 20788560 KNT - 127 Kratom Laudanosine Leu - enkephalin Levomethorphan Levorphanol Lexanopadol Lofentanil Met - enkephalin ( metenkefalin ) Metazocine Metkefamide Mitragynine Mitragynine pseudoindoxyl Morphine N - Phenethyl - 14 - ethoxymetopon Norbuprenorphine NalBzOH Oripavine Oxycodone Oxymorphone Pethidine ( meperidine ) Proglumide Racemethorphan Racemorphan RWJ - 394674 Samidorphan SB - 235863 SNC - 80 SNC - 162 TAN - 67 ( SB - 205,607 ) TH - 030418 Thebaine Thiobromadol ( C - 8813 ) Tonazocine Tramadol TRV250 Xorphanol Zenazocine Antagonists : 4 ', 7 - Dihydroxyflavone 5 ' - NTII 6β - Naltrexol 6β - Naltrexol - d4 α - Santolol β - Chlornaltrexamine Apigenin AT - 076 Axelopran Bevenopran BNTX Catechin Catechin gallate Clocinnamox Diacetylnalorphine Diprenorphine ECG EGC Eluxadoline Epicatechin ICI - 154129 ICI - 174864 LY - 255582 LY - 2196044 Methylnaltrexone Methylnaltrindole N - Benzylnaltrindole Nalmefene Nalorphine Naltrexone Naltriben Naltrindole Naloxone Naringenin Noribogaine Pawhuskin A Quadazocine SDM25N SoRI - 9409 Taxifolin Thienorphine Unknown / unsorted : 18 - MC Cannabidiol Coronaridine Cyproterone acetate Tabernanthine Tetrahydrocannabinol KOR Agonists : 3CS - nalmefene 6 ' - GNTI 8 - CAC 18 - MC 14 - Methoxymetopon β - Chlornaltrexamine β - Funaltrexamine Adrenorphin ( metorphamide ) Akuuamicine Alazocine ( SKF - 10047 ) Allomatrine Apadoline Asimadoline BAM - 12P BAM - 18P BAM - 22P Big dynorphin Bremazocine BRL - 52537 Butorphan Butorphanol BW - 373U86 Cebranopadol Ciprefadol CR665 Cyclazocine Cyclorphan Cyprenorphine Desmetramadol ( desmethyltramadol ) Diamorphine ( heroin ) Diacetylnalorphine Difelikefalin Dihydroetorphine Dihydromorphine Diprenorphine Dynorphin A Dynorphin B ( rimorphin ) Eluxadoline Enadoline Eptazocine Erinacine E Ethylketazocine Etorphine Fedotozine Fentanyl Gemazocine GR - 89696 GR - 103545 Hemorphin - 4 Herkinorin HS665 Hydromorphone HZ - 2 Ibogaine ICI - 199,441 ICI - 204,448 Ketamine Ketazocine Laudanosine Leumorphin ( dynorphin B - 29 ) Levallorphan Levomethorphan Levorphanol Lexanopadol Lofentanil LPK - 26 Lufuradom Matrine MB - 1C - OH Menthol Metazocine Metkefamide Mianserin Mirtazapine Morphine Moxazocine MR - 2034 N - MPPP Nalbuphine Nalbuphine sebacate NalBzOH Nalfurafine Nalmefene Nalodeine ( N - allylnorcodeine ) Nalorphine Naltriben Niravoline Norbuprenorphine Norbuprenorphine - 3 - glucuronide Noribogaine Norketamine Oripavine Oxilorphan Oxycodone Pentazocine Pethidine ( meperidine ) Phenazocine Proxorphan Racemethorphan Racemorphan RB - 64 Salvinorin A ( salvia ) Salvinorin B ethoxymethyl ether Salvinorin B methoxymethyl ether Samidorphan Spiradoline ( U-62,066 ) TH - 030418 Thienorphine Tifluadom Tricyclic antidepressants ( e.g., amitriptyline, desipramine, imipramine, nortriptyline ) U-50,488 U-54,494 A U-69,593 Xorphanol Antagonists : 4 ′ - Hydroxyflavanone 4 ', 7 - Dihydroxyflavone 5 ' - GNTI 6 ' - GNTI 6β - Naltrexol 6β - Naltrexol - d4 β - Chlornaltrexamine Buprenorphine / samidorphan Amentoflavone ANTI Apigenin Arodyne AT - 076 Axelopran AZ - MTAB Binaltorphimine BU09059 Buprenorphine Catechin Catechin gallate CERC - 501 ( LY - 2456302 ) Clocinnamox Cyclofoxy Dezocine DIPPA EGC ECG Epicatechin Hyperoside JDTic LY - 255582 LY - 2196044 LY - 2444296 LY - 2459989 LY - 2795050 MeJDTic Methylnaltrexone ML190 ML350 MR - 2266 N - Fluoropropyl - JDTic Naloxone Naltrexone Naltrindole Naringenin Norbinaltorphimine Noribogaine Pawhuskin A PF - 4455242 RB - 64 Quadazocine Taxifolin UPHIT Zyklophin Unknown / unsorted : Akuammicine Akuammine Coronaridine Cyproterone acetate Dihydroakuuamine Ibogamine Tabernanthine NOP Agonists : ( Arg14, Lys15 ) Nociceptin ( ( pF ) Phe ) Nociceptin ( 1 - 13 ) NH ( Phe Ψ ( CH - NH ) Gly ) Nociceptin ( 1 - 13 ) NH Ac - RYYRWK - NH Ac - RYYRIK - NH BU08070 Buprenorphine Cebranopadol Dihydroetorphine Etorphine JNJ - 19385899 Levomethorphan Levorphanol Levorphanol Lexanopadol MCOPPB MT - 7716 NNC 63 - 0532 Nociceptin ( orphanin FQ ) Nociceptin ( 1 - 11 ) Nociceptin ( 1 - 13 ) NH Norbuprenorphine Racemethorphan Racemorphan Ro64 - 6198 Ro65 - 6570 SCH - 221510 SCH - 486757 SR - 8993 SR - 16435 TH - 030418 Antagonists : ( Nphe ) Nociceptin ( 1 - 13 ) NH AT - 076 BAN - ORL - 24 J - 113397 JTC - 801 LY - 2940094 NalBzOH Nociceptin ( 1 - 7 ) Nocistatin SB - 612111 SR - 16430 Thienorphine Trap - 101 UFP - 101 Unsorted β - Casomorphins Amidorphin BAM - 20P Cytochrophin - 4 Deprolorphin Gliadorphin ( gluteomorphin ) Gluten exorphins Hemorphins Kava constituents MEAGL MEAP NEM Neoendorphins Nepetalactone ( catnip ) Peptide B Peptide E Peptide F Peptide I Rubiscolins Soymorphins Others Enkephalinase inhibitors : Amastatin BL - 2401 Candoxatril D - Phenylalanine Dexecadotril ( retorphan ) Ecadotril ( sinorphan ) Kelatorphan Racecadotril ( acetorphan ) RB - 101 RB - 120 RB - 3007 Opiorphan Selank Semax Spinorphin Thiorphan Tynorphin Ubenimex ( bestatin ) Propeptides : β - Lipotropin ( proendorphin ) Prodynorphin Proenkephalin Pronociceptin Proopiomelanocortin ( POMC ) Others : Kyotorphin ( met - enkephalin releaser / degradation stabilizer ) See also : Receptor / signaling modulators Signaling peptide / protein receptor modulators Retrieved from `` https://en.wikipedia.org/w/index.php?title=Opioid_antagonist&oldid=806985936 '' Categories : Opioid antagonists Hidden categories : CS1 errors : dates All articles with unsourced statements Articles with unsourced statements from October 2017 Talk Contents About Wikipedia Deutsch Suomi Edit links This page was last edited on 25 October 2017, at 07 : 12. 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Question: opioid antagonists work by blocking the actions of
Answer: either blocking multiple opioid receptors, or blocking the MOR