Amitriptyline Systematic ( IUPAC) name 3-(10,11-dihydro-5 H-dibenzo[ a, d]cycloheptene-5-ylidene)- N, N-dimethylpropan-1-amine Clinical data Trade names Amitrip, Elavil, Endep, Levate AHFS/ Drugs.com monograph MedlinePlus a682388 Licence data US FDA: link Pregnancy cat. C ( C AU) ( US) Legal status Prescription Only (S4) ( AU) ℞ -only ( CA) POM ( UK) ℞ -only ( US) Routes Oral, intramuscular Pharmacokinetic data Bioavailability 30–60% due to first pass metabolism Protein binding 96% [1 ] [2 ] [3 ] [4 ] Metabolism Hepatic ( CYP2D6) [1 ] [2 ] [3 ] [4 ] Half-life 22.4 hr (26 hr for active metabolite, nortriptyline) [1 ] [2 ] [3 ] [4 ] Excretion Renal [1 ] [2 ] [3 ] [4 ] Identifiers CAS number 50-48-6 549-18-8 ( hydrochloride) ATC code N06 AA09 PubChem CID 2160 IUPHAR ligand 200 DrugBank DB00321 ChemSpider 2075 UNII 1806D8D52K KEGG D07448 ChEBI CHEBI:2666 ChEMBL CHEMBL629 Chemical data Formula C 20 H 23 N Mol. mass 277.403 g/mol c3cc2c(/C(c1c(cccc1)CC2)=C\CCN(C)C)cc3
Key:KRMDCWKBEZIMAB-UHFFFAOYSA-N (what is this?) (verify) Amitriptyline ( / / Elavil, Endep, Levate and many others) is a tricyclic antidepressant (TCA). It is the most widely used TCA and is an efficacious treatment for major depressive disorder (clinical depression).
It was originally developed by
Merck and was initially approved by the United States Food and Drug Administration (FDA) on 7 April 1961. It is on the [5 ] World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system. [6 ] Medical uses [edit ]
Amitriptyline is used for a number of medical conditions including
major depressive disorder (MDD) which is its only FDA-labelled indication. This is also a [1 ] TGA- and MHRA-labelled indication. [7 ] Some evidence suggests that amitriptyline may have superior efficacy compared to other antidepressants, [8 ] including the [9 ] SSRIs, although it is rarely used as a first-line antidepressant nowadays due to its high degree of toxicity in overdose and generally poorer tolerability than the newer antidepressants such as the [10 ] selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). [7 ]
It is TGA-labelled for
migraine prophylaxis, as it is also is in cases of neuropathic pain disorders, [7 ] fibromyalgia and [11 ] nocturnal enuresis. [7 ] Amitriptyline is a popular [12 ] off-label treatment for irritable bowel syndrome. Although it is most frequently reserved for severe cases of abdominal pain in patients with IBS due to the fact that it needs to be taken regularly to work and has a generally poor tolerability profile, although a firm evidence base supports its efficacy in this indication. [13 ] Amitriptyline can also be used as an [13 ] anticholinergic drug in the treatment of early stage Parkinson disease if depression also needs to be treated. [14 ] Investigational uses [edit ] Adverse effects [edit ]
Adverse effects include the following:
[1 ] [2 ] [3 ] [4 ] [7 ] [8 ] Common (≥1% frequency) [edit ] Weight gain Anticholinergic side effects (it tends to produce more anticholinergic effects than the other TCAs) such as: Constipation Xerostomia (dry mouth) Mydriasis (dilated pupils) Blurred vision Urinary hesitancy Reduced GI motility Anticholinergic delirium (particularly in the elderly and in Parkinson's disease) Dizziness Headache Somnolence (drowsiness) it tends to be a more sedating TCA. [23 ] [24 ] Decreased lacrimation Orthostatic hypotension Sinus tachycardia Impotence Loss of libido Other sexual adverse effects Tremor Sweating Agitation Insomnia Anxiety Confusion Uncommon (0.1–1% frequency) [edit ] Slowed cardiac conduction T wave inversion or flattening (particularly at high doses) Arrhythmias Sinus tachycardia Nausea Hyperglycaemia Gynaecomastia (breast enlargement in men) Breast enlargement and galactorrhoea in females Allergic skin reactions Mania Hypomania Rare (<0.1% frequency) [edit ] Unknown frequency [edit ] Contraindications [edit ]
The following are the known contraindications of amitriptyline.
[4 ] Interactions [edit ]
Amitriptyline is known to interact with:
[3 ] Monoamine oxidase inhibitors as it can potentially induce a serotonin syndrome CYP2D6 inhibitors and substrates such as fluoxetine due to the potential for an increase in plasma concentrations of the drug to be seen. Guanethidine — as it can reduce the antihypertensive effects of this drug. Anticholinergic agents such as benztropine, hyoscine (scopolamine) and atropine. Due to the fact that the two might exacerbate each other's anticholinergic effects, including paralytic ileus and tachycardia. Antipsychotics due to the potential for them to exacerbate the sedative, anticholinergic, epileptogenic and pyrexic (fever-promoting) effects. Also increases the risk of neuroleptic malignant syndrome Cimetidine due to the potential for it to interfere with hepatic metabolism of amitriptyline and hence increasing steady-state concentrations of the drug. Disulfiram due to the potential for the development of delirium ECT may increase the risks associated with this treatment Antithyroid medications — may increase the risk of agranulocytosis Thyroid hormones — potential for increased adverse effects such as CNS stimulation and arrhythmias. Analgesics, such as tramadol due to the potential for an increase in seizure risk. Medications that are subject to gastric inactivation (e.g. levodopa) due to the potential for amitriptyline to delay gastric emptying and reduce intestinal motility Medications that may be subject to increased absorption given more time in the small intestine (e.g. anticoagulants) Serotoninergic agents such as the SSRIs and triptans due to the potential for serotonin syndrome. Overdose [edit ]
The symptoms and the treatment of an overdose are largely the same as for the other TCAs, including the presentation of serotonin syndrome and adverse cardiac effects. The
British National Formulary notes that amitriptyline can be particularly dangerous in overdose, thus it and other tricyclic antidepressants are no longer recommended as first line therapy for depression. Alternative agents, SSRIs and SNRIs are safer in overdose, though they are no more efficacious than TCAs. English folk singer, [8 ] Nick Drake, died from an overdose of Tryptizol in 1974.
The possible symptoms of amitriptyline overdose include:
The treatment of overdose is mostly supportive as there is no specific antidote for amitriptyline overdose.
Activated charcoal may reduce absorption if given within 1–2 hours of ingestion. [3 ] If the affected person is unconscious or have an impaired gag reflex a nasograstic tube may be used to deliver the activated charcoal in the stomach. [3 ] ECG monitoring for cardiac conduction abnormalities is essential and if one is found close monitoring of cardiac function is advised. [3 ] Body temperature should be regulated with measures such as heating blankets if necessary. [3 ] Likewise cardiac arrhythmias can be treated with [3 ] propanolol and should heart failure occur digitalis may be used. Cardiac monitoring is advised for at least five days after the overdose. [3 ] Amitriptyline increases the CNS depressant action but not the anticonvulsant action of barbiturates; therefore, an inhalation anaesthetic or [3 ] diazepam is recommended for control of convulsions. [3 ] Dialysis is of no use due to the high degree of protein binding with amitriptyline. [3 ] Mechanism of action [edit ]
Amitriptyline acts primarily as a
serotonin-norepinephrine reuptake inhibitor, with strong actions on the serotonin transporter and moderate effects on the norepinephrine transporter. [26 ] It has negligible influence on the [27 ] dopamine transporter and therefore does not affect dopamine reuptake, being nearly 1,000 times weaker on it than on serotonin. It is metabolised to [27 ] nortriptyline — a more potent and selective norepinephrine reuptake inhibitor — which may compliment its effects on norepinephrine reuptake. [3 ]
Amitriptyline additionally functions as a
5-HT, 2A 5-HT, 2C 5-HT, 3 5-HT, 6 5-HT, 7 α, 1-adrenergic H, 1 H, 2 [28 ] H, 4 [29 ] and [30 ] mACh receptor antagonist, and σ 1 receptor agonist. [31 ] [32 ] [33 ] It has also been shown to be a relatively weak [34 ] NMDA receptor negative allosteric modulator at the same binding site as phencyclidine. Amitriptyline inhibits [35 ] sodium channels, , and L-type calcium channels K, v1.1 K, and v7.2 K v7.3 voltage-gated potassium channels, and therefore acts as a sodium, calcium, and potassium channel blocker as well. [36 ] [37 ]
Recently, amitriptyline has been demonstrated to act as an
agonist of the TrkA and TrkB receptors. It promotes the [38 ] heterodimerization of these proteins in the absence of NGF and has potent neurotrophic activity both in-vivo and in-vitro in mouse models. [38 ] These are the same receptors [39 ] BDNF activates, an endogenous neurotrophin with powerful antidepressant effects, and as such this property may contribute significantly to its therapeutic efficacy against depression. Amitriptyline also acts as FIASMA (functional inhibitor of acid sphingomyelinase). [40 ] Pharmacokinetics [edit ]
Amitriptyline is readily absorbed from the gastrointestinal tract and is extensively metabolised on first-pass through the liver.
It is metabolised mostly via [3 ] CYP2D6, CYP3A4, CYP2C19-mediated N-demethylation into nortriptyline, which is another [3 ] tricyclic antidepressant in its own right. It is 96% bound to plasma proteins, nortriptyline is 93-95% bound to plasma proteins. [41 ] [3 ] It is mostly excreted in the urine (around 30-50%) as metabolites either free or as glucuronide and sulfate conjugates. [42 ] Small amounts are also excreted in faeces. [3 ] [2 ] Brand names [edit ]
Brand names include (just including those used in English-speaking countries with † to indicate discontinued brands):
[41 ] [43 ] Amirol ( NZ) Amit ( IN) Amitone ( IN) Amitor ( IN) Amitrip ( AU,† IN, NZ) Amitriptyline ( UK) Amitriptyline Hydrochloride Caraco ( US) Amitriptyline Hydrochloride Mutual ( US) Amitriptyline Hydrochloride Mylan ( US) Amitriptyline Hydrochloride Sandoz ( US) Amitriptyline Hydrochloride Vintage ( US) Amitriptyline Hydrochloride ( UK) Amitrol† ( AU) Amrea ( IN) Amypres ( IN) Apo-Amitriptyline ( CA, HK, SG) Crypton ( IN) Elavil ( CA, UK,† US†) Eliwel ( IN) Endep ( AU, HK,† ZA,† US†) Enovil† ( US) Gentrip ( IN) Kamitrin ( IN) Latilin ( IN) Levate ( US) Maxitrip ( IN) Mitryp ( IN) Mitryp-10 ( IN) Odep ( IN) Qualitriptine ( HK) Sandoz Amitriptyline ( ZA) Saroten ( CH) Sarotena ( IN) Tadamit ( IN) Trepiline ( ZA) Tripta ( SG) Tryptanol ( ZA) Tryptomer ( IN) Notes [edit ] ^ These K i values are averaged binding affinities towards cloned human receptors when available. ^ As with amitriptyline, these K ivalues are averaged binding affinities towards cloned human receptors when available. See also [edit ] References [edit ] ^ a b c d e f "AMITRIPTYLINE HYDROCHLORIDE tablet, film coated [Dispensing Solutions, Inc.]". DailyMed. Dispensing Solutions, Inc. September 2013 . Retrieved 1 December 2013. ^ a b c d e f g "Levate (amitriptyline), dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD . Retrieved 1 December 2013. ^ a b c d e f g h i j k l m n o p q r s t u "Endep Amitriptyline hydrochloride" (PDF). TGA eBusiness Services. Alphapharm Pty Limited. 10 December 2012 . Retrieved 1 December 2013. ^ a b c d e f "Amitriptyline Tablets BP 50mg - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Actavis UK Ltd. 24 March 2013 . Retrieved 1 December 2013. ^ Fangmann P, Assion HJ, Juckel G, González CA, López-Muñoz F (February 2008). "Half a century of antidepressant drugs: on the clinical introduction of monoamine oxidase inhibitors, tricyclics, and tetracyclics. Part II: tricyclics and tetracyclics". Journal of Clinical Psychopharmacology 28 (1): 1–4. doi: 10.1097/jcp.0b013e3181627b60. PMID 18204333. ^ "WHO Model List of Essential Medicines". World Health Organization. October 2013 . Retrieved 22 April 2014. ^ a b c d e f g Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3. ^ a b c Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8. ^ Barbui C, Hotopf M (February 2001). "Amitriptyline v. the rest: still the leading antidepressant after 40 years of randomised controlled trials". The British Journal of Psychiatry : the Journal of Mental Science 178 (2): 129–144. doi: 10.1192/bjp.178.2.129. PMID 11157426. ^ Anderson IM (April 2000). "Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efﬁcacy and tolerability". 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Retrieved 2013-02-16. ^ Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, Mühle C, Terfloth L, Groemer TW, Spitzer GM, Liedl KR, Gulbins E, Tripal P (2011). "Identification of novel functional inhibitors of acid sphingomyelinase". In Riezman, Howard. PLoS ONE 6 (8): e23852. doi: 10.1371/journal.pone.0023852. PMC 3166082. PMID 21909365. ^ a b "Amitriptyline". Martindale: The Complete Drug Reference (London, UK: Pharmaceutical Press). 30 January 2013 . Retrieved 2 December 2013. ^ "Pamelor, Aventyl (nortriptyline) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD . Retrieved 2 December 2013. ^ "Amitriptyline". Drugs.com . Retrieved 2 December 2013. Further reading [edit ]
Agonists: 77-LH-28-1 AC-42 AC-260,584 Aceclidine Acetylcholine AF30 AF150(S) AF267B AFDX-384 Alvameline AQRA-741 Arecoline Bethanechol Butyrylcholine Carbachol CDD-0034 CDD-0078 CDD-0097 CDD-0098 CDD-0102 Cevimeline Choline cis-Dioxolane Ethoxysebacylcholine LY-593,039 L-689,660 LY-2,033,298 McNA343 Methacholine Milameline Muscarine NGX-267 Ocvimeline Oxotremorine PD-151,832 Pilocarpine RS86 Sabcomeline SDZ 210-086 Sebacylcholine Suberylcholine Talsaclidine Tazomeline Thiopilocarpine Vedaclidine VU-0029767 VU-0090157 VU-0152099 VU-0152100 VU-0238429 WAY-132,983 Xanomeline YM-796 Antagonists: 3-Quinuclidinyl Benzilate 4-DAMP Aclidinium Bromide Anisodamine Anisodine Atropine Atropine Methonitrate Benactyzine Benzatropine/Benztropine Benzydamine BIBN 99 Biperiden Bornaprine CAR-226,086 CAR-301,060 CAR-302,196 CAR-302,282 CAR-302,368 CAR-302,537 CAR-302,668 CS-27349 Cyclobenzaprine Cyclopentolate Darifenacin DAU-5884 Dimethindene Dexetimide DIBD Dicyclomine/Dicycloverine Ditran EA-3167 EA-3443 EA-3580 EA-3834 Etanautine Etybenzatropine/Ethylbenztropine Flavoxate Himbacine HL-031,120 Ipratropium bromide J-104,129 Hyoscyamine Mamba Toxin 3 Mamba Toxin 7 Mazaticol Mebeverine Methoctramine Metixene N-Ethyl-3-Piperidyl Benzilate N-Methyl-3-Piperidyl Benzilate Orphenadrine Otenzepad Oxybutynin PBID PD-102,807 PD-0298029 Phenglutarimide Phenyltoloxamine Pirenzepine Piroheptine Procyclidine Profenamine RU-47,213 SCH-57,790 SCH-72,788 SCH-217,443 Scopolamine/Hyoscine Solifenacin Telenzepine Tiotropium bromide Tolterodine Trihexyphenidyl Tripitamine Tropatepine Tropicamide WIN-2299 Xanomeline Zamifenacin; Others: 1st Generation Antihistamines ( Brompheniramine chlorphenamine cyproheptadine dimenhydrinate diphenhydramine doxylamine mepyramine/ pyrilamine phenindamine pheniramine tripelennamine triprolidine, etc) Tricyclic Antidepressants ( Amitriptyline doxepin trimipramine, etc) Tetracyclic Antidepressants ( Amoxapine maprotiline, etc) Typical Antipsychotics ( Chlorpromazine thioridazine, etc) Atypical Antipsychotics ( Clozapine olanzapine, etc.) Agonists: 5-HIAA A-84,543 A-366,833 A-582,941 A-867,744 ABT-202 ABT-418 ABT-560 ABT-894 Acetylcholine Altinicline Anabasine Anatoxin-a AR-R17779 Butinoline Butyrylcholine Carbachol Choline Cotinine Cytisine Decamethonium Desformylflustrabromine Dianicline Dimethylphenylpiperazinium Epibatidine Epiboxidine Ethanol Ethoxysebacylcholine EVP-4473 EVP-6124 Galantamine GTS-21 Ispronicline Lobeline MEM-63,908/RG-3487 Nicotine NS-1738 PHA-543,613 PHA-709,829 PNU-120,596 PNU-282,987 Pozanicline Rivanicline RJR-2429 Sazetidine A Sebacylcholine SIB-1508Y SIB-1553A SSR-180,711 Suberylcholine Suxamethonium/Succinylcholine TC-1698 TC-1734 TC-1827 TC-2216 TC-5214 TC-5619 TC-6683 Tebanicline Tropisetron UB-165 Varenicline WAY-317,538 XY-4083 Antagonists: 18-Methoxycoronaridine α-Bungarotoxin α-Conotoxin Alcuronium Amantadine Anatruxonium Atracurium Bupropion Chandonium Chlorisondamine Cisatracurium Coclaurine Coronaridine Dacuronium Decamethonium Dextromethorphan Dextropropoxyphene Dextrorphan Diadonium DHβE Dihydrochandonium Dimethyltubocurarine/Metocurine Dipyrandium Dizocilpine/MK-801 Doxacurium Esketamine Fazadinium Gallamine Hexafluronium Hexamethonium/Benzohexonium Ibogaine Isoflurane Ketamine Kynurenic acid Laudexium/Laudolissin Levacetylmethadol Malouetine Mecamylamine Memantine Methadone ( Levomethadone) Methorphan/Racemethorphan Methyllycaconitine Metocurine Mivacurium Morphanol/Racemorphan Neramexane Nitrous Oxide Pancuronium Pempidine Pentamine Pentolinium Phencyclidine Pipecuronium Radafaxine Rapacuronium Rocuronium Surugatoxin Thiocolchicoside Toxiferine Trimethaphan Tropeinium Tubocurarine Vecuronium Xenon
Agonists: Glutamate/acite site competitive agonists: Aspartate Glutamate Homoquinolinic acid Ibotenic acid NMDA Quinolinic acid Tetrazolylglycine; Glycine site agonists: ACBD ACPC ACPD Alanine CCG Cycloserine DHPG Fluoroalanine Glycine GLYX-13 HA-966 L-687,414 Milacemide Sarcosine Serine Tetrazolylglycine; Polyamine site agonists: Acamprosate Spermidine Spermine Antagonists: Competitive antagonists: AP5 (APV) AP7 CGP-37849 CGP-39551 CGP-39653 CGP-40116 CGS-19755 CPP LY-233,053 LY-235,959 LY-274,614 MDL-100,453 Midafotel (d-CPPene) NPC-12,626 NPC-17,742 PBPD PEAQX Perzinfotel PPDA SDZ-220581 Selfotel; Noncompetitive antagonists: ARR-15,896 Caroverine Dexanabinol FPL-12495 FR-115,427 Hodgkinsine Magnesium MDL-27,266 NPS-1506 Psychotridine Zinc; Uncompetitive pore blockers: 2-MDP 3-MeO-PCP 8A-PDHQ Alaproclate Amantadine Aptiganel ARL-12,495 ARL-15,896-AR ARL-16,247 Budipine Delucemine Dexoxadrol Dextrallorphan Dieticyclidine Dizocilpine Endopsychosin Esketamine Etoxadrol Eticyclidine Gacyclidine Ibogaine Indantadol Ketamine Ketobemidone Lanicemine Loperamide Memantine Meperidine (Pethidine) Methadone ( Levomethadone) Methorphan ( Dextromethorphan Levomethorphan) Methoxetamine Milnacipran Morphanol ( Dextrorphan Levorphanol) NEFA Neramexane Nitromemantine Nitrous oxide Noribogaine Orphenadrine PCPr Phencyclamine Phencyclidine Propoxyphene Remacemide Rhynchophylline Riluzole Rimantadine Rolicyclidine Sabeluzole Tenocyclidine Tiletamine Tramadol Xenon; Glycine site antagonists: ACEA-1021 ACEA-1328 ACC Carisoprodol CGP-39653 CKA DCKA Felbamate Gavestinel GV-196,771 Kynurenic acid L-689,560 L-701,324 Lacosamide Licostinel LU-73,068 MDL-105,519 Meprobamate MRZ 2/576 PNQX ZD-9379; NR2B subunit antagonists: Besonprodil CO-101,244 (PD-174,494) CP-101,606 Eliprodil Haloperidol Ifenprodil Isoxsuprine Nylidrin Ro8-4304 Ro25-6981 Traxoprodil; Polyamine site antagonists: Arcaine Co 101676 Diaminopropane Acamprosate Diethylenetriamine Huperzine A Putrescine Ro 25-6981; Unclassified/unsorted antagonists: Chloroform Diethyl ether Diphenidine Enflurane Ethanol (alcohol) Halothane Isoflurane Methoxyflurane Toluene Trichloroethane Trichloroethanol Trichloroethylene Xylene Metabotropic
Agonists: Non-selective: L-AP4; mGlu4-selective: PHCCC VU-001,171 VU-0155,041; mGlu7-selective: AMN082; mGlu8-selective: DCPG Antagonists: Non-selective: CPPG MAP4 MSOP MPPG MTPG UBP-1112; mGlu7-selective: MMPIP Transporter inhibitors Others
Ungrouped: Belarizine Efletirizine Elbanizine Flotrenizine Medrylamine Napactadine Pibaxizine Tagorizine Trelnarizine Trenizine Vapitadine Miscellaneous: Tricyclic antidepressants ( amitriptyline, doxepin, trimipramine, etc) Tetracyclic antidepressants ( mianserin, mirtazapine, etc) Typical antipsychotics ( chlorpromazine, thioridazine, etc) Atypical antipsychotics ( clozapine, olanzapine, quetiapine, etc) Transporter Enzyme Others
Agonists: Azapirones: Alnespirone Binospirone Buspirone Enilospirone Eptapirone Gepirone Ipsapirone Perospirone Revospirone Tandospirone Tiospirone Umespirone Zalospirone; Antidepressants: Etoperidone Nefazodone Trazodone Vortioxetine; Antipsychotics: Aripiprazole Asenapine Clozapine Quetiapine Ziprasidone; Ergolines: Dihydroergotamine Bromocriptine Ergotamine Lisuride Methysergide LSD; Tryptamines: 5-CT 5-MeO-DMT 5-MT Bufotenin DMT Indorenate Psilocin Psilocybin; Others: 8-OH-DPAT Adatanserin Bay R 1531 Befiradol BMY-14802 Cannabidiol Dimemebfe Ebalzotan Eltoprazine F-11,461 F-12,826 F-13,714 F-14,679 F-15,063 F-15,599 Flesinoxan Flibanserin Lesopitron LY-293,284 LY-301,317 MKC-242 Naluzotan NBUMP Osemozotan Oxaflozane Pardoprunox Piclozotan Rauwolscine Repinotan Roxindole RU-24,969 S 14,506 S-14,671 S-15,535 Sarizotan SSR-181,507 Sunepitron U-92,016-A Urapidil Vilazodone Xaliproden Yohimbine Antagonists: Antipsychotics: Iloperidone Risperidone Sertindole; Beta blockers: Alprenolol Cyanopindolol Iodocyanopindolol Oxprenolol Pindobind Pindolol Propranolol Tertatolol; Others: AV965 BMY-7,378 CSP-2503 Dotarizine Flopropione GR-46611 Isamoltane Lecozotan Mefway Metitepine/Methiothepin MPPF NAN-190 Robalzotan S-15535 SB-649,915 SDZ 216-525 Spiperone Spiramide Spiroxatrine UH-301 WAY-100,135 WAY-100,635 Xylamidine Agonists: Lysergamides: Dihydroergotamine Methysergide; Triptans: Almotriptan Avitriptan Eletriptan Frovatriptan Naratriptan Rizatriptan Sumatriptan Zolmitriptan; Tryptamines: 5-CT 5-Ethyl-DMT 5-MT 5-(Nonyloxy)tryptamine; Others: CP-135,807 Bromocriptine CP-286,601 GR-46611 L-694,247 L-772,405 PNU-109,291 PNU-142633 Antagonists: Lysergamides: Metergoline; Others: Alniditan BRL-15,572 Elzasonan GR-127,935 Ketanserin LY-310,762 LY-367,642 LY-456,219 LY-456,220 Metitepine/Methiothepin Ritanserin Yohimbine Ziprasidone
Agonists: Phenethylamines: 2C-B 2C-E 2C-I 2C-T-2 2C-T-7 2C-T-21 DOB DOC DOI DOM MDA MDMA Mescaline; Piperazines: Aripiprazole mCPP TFMPP; Tryptamines: 5-CT 5-MeO-α-ET 5-MeO-α-MT 5-MeO-DET 5-MeO-DiPT 5-MeO-DMT 5-MeO-DPT 5-MT α-ET α-Methyl-5-HT α-MT Bufotenin DET DiPT DMT DPT Psilocin Psilocybin; Others: A-372,159 AL-38022A Alstonine Bromocriptine CP-809,101 Dimemebfe Lorcaserin Medifoxamine MK-212 Org 12,962 ORG-37,684 Oxaflozane PHA-57378 PNU-22394 PNU-181731 Ro60-0175 Ro60-0213 Vabicaserin WAY-629 WAY-161,503 YM-348 Antagonists: Atypical antipsychotics: Clorotepine Clozapine Iloperidone Melperone Olanzapine Paliperidone Quetiapine Risperidone Sertindole Ziprasidone Zotepine; Typical antipsychotics: Chlorpromazine Loxapine Pimozide Pipamperone; Antidepressants: Agomelatine Amitriptyline Amoxapine Aptazapine Etoperidone Fluoxetine Mianserin Mirtazapine Nefazodone Nortriptyline Tedatioxetine Trazodone; Others: Adatanserin CEPC Cinanserin Cyproheptadine Deramciclane Dotarizine Eltoprazine Esmirtazapine FR-260,010 Ketanserin Ketotifen Latrepirdine Metitepine/Methiothepin Methysergide Pizotifen Ritanserin RS-102,221 S-14,671 SB-200,646 SB-206,553 SB-221,284 SB-228,357 SB-242,084 SB-243,213 SDZ SER-082 Xylamidine
Agonists: Lysergamides: Dihydroergotamine Ergotamine Lisuride LSD Mesulergine Metergoline Methysergide; Tryptamines: 2-Methyl-5-HT 5-BT 5-CT 5-MT Bufotenin E-6801 E-6837 EMD-386,088 EMDT LY-586,713 N-Methyl-5-HT Tryptamine; Others: WAY-181,187 WAY-208,466 Antagonists: Antidepressants: Amitriptyline Amoxapine Clomipramine Doxepin Mianserin Nortriptyline; Atypical antipsychotics: Aripiprazole Asenapine Clorotepine Clozapine Fluperlapine Iloperidone Olanzapine Tiospirone; Typical antipsychotics: Chlorpromazine Loxapine; Others: BGC20-760 BVT-5182 BVT-74316 Cerlapirdine EGIS-12,233 GW-742,457 Ketanserin Latrepirdine Lu AE58054 Metitepine/Methiothepin MS-245 PRX-07034 Ritanserin Ro04-6790 Ro 63-0563 SB-258,585 SB-271,046 SB-357,134 SB-399,885 SB-742,457 Agonists: Lysergamides: LSD; Tryptamines: 5-CT 5-MT Bufotenin; Others: 8-OH-DPAT AS-19 Bifeprunox E-55888 LP-12 LP-44 RU-24,969 Sarizotan Antagonists: Lysergamides: 2-Bromo-LSD Bromocriptine Dihydroergotamine Ergotamine Mesulergine Metergoline Methysergide; Antidepressants: Amitriptyline Amoxapine Clomipramine Imipramine Maprotiline Mianserin; Atypical antipsychotics: Amisulpride Aripiprazole Asenapine Clorotepine Clozapine Olanzapine Risperidone Sertindole Tiospirone Ziprasidone Zotepine; Typical antipsychotics: Chlorpromazine Loxapine; Pimozide; Others: Butaclamol EGIS-12,233 Ketanserin LY-215,840 Metitepine/Methiothepin Ritanserin SB-258,719 SB-258,741 SB-269,970 SB-656,104 SB-656,104-A SB-691,673 SLV-313 SLV-314 Spiperone SSR-181,507 Vortioxetine