Alosetron
|
Systematic (IUPAC) name |
5-methyl-2-[(4-methyl-1H-imidazol-5-yl)methyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-1-one |
Clinical data |
Trade names |
Lotronex |
AHFS/Drugs.com |
monograph |
MedlinePlus |
a601230 |
Pregnancy cat. |
B (U.S.) |
Legal status |
℞-only (U.S.) |
Routes |
Oral |
Pharmacokinetic data |
Bioavailability |
50–60% |
Protein binding |
82% |
Metabolism |
Hepatic (including CYP2C9, CYP3A4 and CYP1A2) |
Half-life |
1.5–1.7 hours |
Excretion |
Renal 73%, faecal 24% |
Identifiers |
CAS number |
122852-42-0 Y |
ATC code |
A03AE01 |
PubChem |
CID 2099 |
IUPHAR ligand |
2296 |
DrugBank |
DB00969 |
ChemSpider |
2015 Y |
UNII |
13Z9HTH115 Y |
KEGG |
D07129 Y |
ChEBI |
CHEBI:253342 Y |
ChEMBL |
CHEMBL1110 Y |
Chemical data |
Formula |
C17H18N4O |
Mol. mass |
294.351 g/mol |
SMILES
- O=C1N(CCc3c1c2ccccc2n3C)Cc4ncnc4C
|
InChI
-
InChI=1S/C17H18N4O/c1-11-13(19-10-18-11)9-21-8-7-15-16(17(21)22)12-5-3-4-6-14(12)20(15)2/h3-6,10H,7-9H2,1-2H3,(H,18,19) Y
Key:JSWZEAMFRNKZNL-UHFFFAOYSA-N Y
|
Y (what is this?) (verify)
|
Alosetron hydrochloride (initial brand name: Lotronex; originator: GSK) is a 5-HT3 antagonist used for the management of severe diarrhea-predominant irritable bowel syndrome (IBS) in women only. It is currently marketed by Prometheus Laboratories Inc. (San Diego), also under the trade name Lotronex. Alosetron was withdrawn from the market in 2000 owing to the occurrence of serious life-threatening gastrointestinal adverse effects, but was reintroduced in 2002 with availability and use restricted.
Contents
- 1 Approval history
- 2 Indications
- 3 Contraindications
- 4 Efficacy
- 5 Adverse effects
- 6 Mechanism of action
- 7 References
Approval history[edit source | edit]
Alosetron was originally approved by the U.S. Food and Drug Administration (FDA) on February 9, 2000,[1] after a seven month review.[2] At the time of the initial approval U.S. Food and Drug Administration (FDA) reviewers found that alosetron improved symptoms in 10% to 20% of patients.[3]
Shipment to pharmacies started in March, 2000. On July 17, a health professional filed a report with the FDA on the death of a 50-year-old woman who suffered mesenteric ischemia. The report identified alosetron as the "primary suspect" in the death.[4]
Alosetron was withdrawn from the market voluntarily by GlaxoWellcome on November 28, 2000 owing to the occurrence of serious life-threatening gastrointestinal adverse effects, including 5 deaths and additional bowel surgeries.[2] The FDA said it had reports of 49 cases of ischemic colitis and 21 cases of "severe constipation" and that ten of the 70 patients underwent surgeries and 34 others were examined at hospitals and released without surgery. Through November 17, 2000, pharmacists had filled 474,115 prescriptions for Alosetron.[2] Severe adverse events continued to be reported, with a final total of 84 instances of ischaemic colitis, 113 of severe constipation, 143 admissions to hospital, and 7 deaths.[5]
Patient advocacy groups, most notably the Lotronex Action Group and the International Foundation for Functional Gastrointestinal Disorders (IFFGD) lobbied for the drug's return. Public Citizen Health Research Group, another patient advocacy group, opposed the reintroduction.[6][7]
On June 7, 2002, the FDA announced the approval of a supplemental New Drug Application (sNDA) that allows restricted marketing of Lotronex (alosetron hydrochloride), to treat only women with severe diarrhea-predominant irritable bowel syndrome (IBS).[8] It was the first drug ever returned to the U.S. market after withdrawal for safety concerns.[9][10]
It is not known whether alosetron has been filed for registration in the EU.
GSK sold Lotronex to the Californian corporation Prometheus in late 2007.[11]
Criticism of the FDA[edit source | edit]
In 2001, the editor of the renowned medical journal The Lancet, Richard Horton, criticized the FDA's handling of alosetron in an unusually sharp language.[12] Horton argued that the treatment of a non-fatal condition did not justify the use of a drug with potentially lethal side effects, and that the FDA should have revoked the approval for alosetron sooner when postmarketing surveillance revealed that many patients had suffered constipation necessitating surgical intervention and ischaemic colitis. He asserted that FDA officials were improperly motivated to maintain and reinstate the approval for alosetron because of the extent to which the FDA's Center for Drug Evaluation and Research is funded by user fees paid by pharmaceutical manufacturers, and that the reinstatement of alosetron was negotiated in confidential meetings with representatives of GlaxoSmithKline.
An article published in the British Medical Journal (BMJ) noted: "By allowing the marketing of alosetron, a drug that poses a serious and significant public health concern according to its own terms, the FDA failed in its mission."[13] Others have argued that the approval process of Lotronex was an example of regulatory capture.[7]
Indications[edit source | edit]
Alosetron is indicated only for women with severe diarrhea-predominant irritable bowel syndrome (IBS) who have: chronic IBS symptoms (generally lasting 6 months or longer), had anatomic or biochemical abnormalities of the gastrointestinal tract excluded, and not responded adequately to conventional therapy. Severe IBS includes diarrhea and 1 or more of the following: frequent and severe abdominal pain/discomfort, frequent bowel urgency or fecal incontinence, disability or restriction of daily activities due to IBS.[14]
Contraindications[edit source | edit]
Lotronex's prescribing information brochure states that alosetron should not be initiated in patients with constipation. Other contraindications are: history of chronic or severe constipation or sequelae from constipation; intestinal obstruction, stricture, toxic megacolon, gastrointestinal perforation, and/or adhesions, ischemic colitis, impaired intestinal circulation, thrombophlebitis, or hypercoagulable state; Crohn's disease or ulcerative colitis; diverticulitis; severe hepatic impairment. Concomitant use of fluvoxamine is also contraindicated.[14]
Efficacy[edit source | edit]
The phase III trial for approval was published in 2000 as an industry-funded randomised, placebo-controlled trial (PCT). Its authors found 1 mg alosetron, taken orally twice daily for 12 weeks, was associated with a 12% (CI 4.7-19.2) improvement in relief from abdominal pain and discomfort associated with diarrhoea-predominant patients.[15] The prescription of alosetron is currently approved in the U.S. at .5 and 1 mg.[7]
The FDA Medical Officer's Review, dated November 4, 1999, noted: “Patients considered by investigators to fit the diarrhea-predominant subtype had at baseline… stool consistency values that were neither loose nor watery”.[16] The FDA's Gastrointestinal Drugs Advisory Committee referred to the drug's efficacy as "modest", highlighting that the placebo brought relief on the primary outcome measure to 40–50% of women.[7]
Adverse effects[edit source | edit]
Alosetron was withdrawn in 2000 following the association of alosetron with serious life-threatening gastrointestinal adverse effects. The cumulative incidence of ischaemic colitis was 2 in 1000, while serious complications arising from constipation (obstruction, perforation, impaction, toxic megacolon, secondary colonic ischaemia, death) was 1 in 1000.[14] A 1999 review performed by FDA medical officer John Senior, indicated that 27% of patients experienced constipation.[4] The phase III trial reported constipation occurred in 30% and 3% of patients in the alosetron and placebo groups, respectively. It was cited as the most important reason for patients dropping out of the study.[15]
Mechanism of action[edit source | edit]
Alosetron has an antagonist action on the 5-HT3 receptors of the enteric nervous system of the gastrointestinal tract. While being a 5-HT3 antagonist like ondansetron, it is not classified or approved as an antiemetic. Since stimulation of 5-HT3 receptors is positively correlated with gastrointestinal motility, alosetron's 5-HT3 antagonism slows the movement of fecal matter through the large intestine, increasing the extent to which water is absorbed, and decreasing the moisture and volume of the remaining waste products.[14]
References[edit source | edit]
- ^ U.S. Food and Drug Administration. "Drug Details". Retrieved 11 December 2012.
- ^ a b c Willman, David (29 November 2000). "Drug Lotronex Pulled Over Safety Fears". The Los Angeles Times. Retrieved 11 December 2012.
- ^ Willman, David (20 December 2000). "Officer Foresaw Deadly Effects". The Los Angeles Times. Retrieved 11 December 2012.
- ^ a b Willman, David (2 November 2000). "FDA Minimized Issue of Lotronex's Safety". The Los Angeles Times. Retrieved 11 December 2012.
- ^ CENTER FOR DRUG EVALUATION AND RESEARCH (23 April 2002). "GASTROINTESTINAL DRUGS ADVISORY COMMITTEE AND DRUG SAFETY AND RISK MANAGEMENT SUBCOMMITTEE OF THE ADVISORY COMMITTEE FOR PHARMACEUTICAL SCIENCE". U.S. Food and Drug Administration. Retrieved 11 December 2012.
- ^ Grady, Denise (23 April 2002). "Appeals Prompt U.S. Agency to Consider Allowing Sales of Diarrhea Drug Linked to Deaths". The New York Times. Retrieved 11 December 2012.
- ^ a b c d Moynihan, Ray (14 September 2002). "Alosetron: a case study in regulatory capture, or a victory for patients' rights?". The British Medical Journal 325 (7364): 592–595. PMC 1124108. PMID 12228140. Retrieved 11 December 2012.
- ^ U.S. Food and Drug Administration. "Lotronex (alosetron hydrochloride) Information". U.S. Food and Drug Administration. Retrieved 11 December 2012.
- ^ Pollack, A (2006-03-09). "F.D.A. Panel Recommends M.S. Drug Despite Lethal Risk". The New York Times. Retrieved 2008-03-13.
- ^ Grady, Denise (8 June 2002). "U.S. Lets Drug Tied to Deaths Back on Market". The New York Times. Retrieved 11 December 2012.
- ^ Prometheus Laboratories Inc. Press Release of 7 November 2007. Retrieved on 27 August 2008.
- ^ Horton, R. (2001). "Lotronex and the FDA: a fatal erosion of integrity". The Lancet 357 (9268): 1544–1545. doi:10.1016/S0140-6736(00)04776-0. edit
- ^ Lièvre, Michel (14 September 2002). "Alosetron for irritable bowel syndrome". The British Medical Journal 325 (7364): 555–556. PMC 1124090. PMID 12228116. Retrieved 11 December 2012.
- ^ a b c d "HIGHLIGHTS OF PRESCRIBING INFORMATION". Prometheus Laboratories Inc. April 2008. Retrieved 11 December 2012.
- ^ a b Camilleri, M.; Northcutt A.R., Kong S., Dukes G.E., McSorley D., Mangel A.W. (25 March 2000). "Efficacy and safety of alosetron in women with irritable bowel syndrome: a randomised, placebo-controlled trial.". The Lancet 355 (1035): 1035–40. doi:10.1016/S0140-6736(00)02033-X. PMID 10744088.
- ^ Barbehenn, Elizabeth; Peter Lurie, Sidney M. Wolfe (9 December 2000). "Alosetron for irritable bowel syndrome". The Lancet 356 (9246): 2009. doi:10.1016/S0140-6736(05)72978-0. Retrieved 11 December 2012.
Drugs for functional gastrointestinal disorders (A03)
|
|
Drugs for
functional
bowel disorders |
Antimuscarinics
|
Tertiary
amino group
|
- Oxyphencyclimine
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|
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Phosphodiesterase
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Acting on
serotonin receptors
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Other
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Propulsives |
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|
|
|
anat (t, g, p)/phys/devp/enzy
|
noco/cong/tumr, sysi/epon
|
proc, drug (A2A/2B/3/4/5/6/7/14/16), blte
|
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|
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Serotonergics
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5-HT1 receptor ligands
|
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5-HT1A
|
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- SSR-181,507
- Sunepitron
- U-92,016-A
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Antagonists: Antipsychotics: Iloperidone
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- UH-301
- WAY-100,135
- WAY-100,635
- Xylamidine
|
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5-HT1B
|
- Agonists: Lysergamides: Dihydroergotamine
- Ergotamine
- Methysergide; Piperazines: Eltoprazine
- TFMPP; Triptans: Avitriptan
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Antagonists: Lysergamides: Metergoline; Others: AR-A000002
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- Isamoltane
- Metitepine/Methiothepin
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- SB-224,289
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|
|
5-HT1D
|
- Agonists: Lysergamides: Dihydroergotamine
- Methysergide; Triptans: Almotriptan
- Avitriptan
- Eletriptan
- Frovatriptan
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- 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
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5-HT1E
|
- Agonists: Lysergamides: Methysergide; Triptans: Eletriptan; Tryptamines: BRL-54443
- Tryptamine
Antagonists: Metitepine/Methiothepin
|
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5-HT1F
|
- Agonists: Triptans: Eletriptan
- Naratriptan
- Sumatriptan; Tryptamines: 5-MT; Others: BRL-54443
- Bromocriptine
- Lasmiditan
- LY-334,370
Antagonists: Metitepine/Methiothepin
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5-HT2 receptor ligands
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5-HT2A
|
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5-HT2B
|
- Agonists: Oxazolines: 4-Methylaminorex
- Aminorex; Phenethylamines: Chlorphentermine
- Cloforex
- DOB
- DOC
- DOI
- DOM
- Fenfluramine (Dexfenfluramine, Levofenfluramine)
- MDA
- MDMA
- Norfenfluramine; Tryptamines: 5-CT
- 5-MT
- α-Methyl-5-HT; Others: BW-723C86
- Bromocriptine
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- mCPP
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- PNU-22394
- Ro60-0175
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- EGIS-7625
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- SB-200,646
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- SB-221,284
- SB-228,357
- SDZ SER-082
- Tegaserod
- Yohimbine
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5-HT2C
|
- Agonists: Phenethylamines: 2C-B
- 2C-E
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- 2C-T-2
- 2C-T-7
- 2C-T-21
- DOB
- DOC
- DOI
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- mCPP
- TFMPP; Tryptamines: 5-CT
- 5-MeO-α-ET
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- 5-MeO-DPT
- 5-MT
- α-ET
- α-Methyl-5-HT
- α-MT
- Bufotenin
- DET
- DiPT
- DMT
- DPT
- Psilocin
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- Bromocriptine
- AL-38022A
- CP-809,101
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- MK-212
- Org 12,962
- ORG-37,684
- Oxaflozane
- PNU-22394
- Ro60-0175
- Ro60-0213
- Vabicaserin
- WAY-629
- WAY-161,503
- YM-348
Antagonists: Atypical antipsychotics: Clorotepine
- Clozapine
- Iloperidone
- Melperone
- Olanzapine
- Paliperidone
- Pimozide
- Quetiapine
- Risperidone
- Sertindole
- Ziprasidone
- Zotepine; Typical antipsychotics: Chlorpromazine
- Loxapine
- Pipamperone; Antidepressants: Agomelatine
- Amitriptyline
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- Fluoxetine
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- Nortriptyline
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- FR-260,010
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- SB-206,553
- SB-221,284
- SB-228,357
- SB-242,084
- SB-243,213
- SDZ SER-082
- Xylamidine
|
|
|
|
- 5-HT3
- 5-HT4
- 5-HT5
- 5-HT6
- 5-HT7 ligands
|
|
5-HT3
|
- Agonists: Piperazines: BZP
- Quipazine; Tryptamines: 2-Methyl-5-HT
- 5-CT; Others: Chlorophenylbiguanide
- Butanol
- Ethanol
- Halothane
- Isoflurane
- RS-56812
- SR-57,227
- SR-57,227-A
- Toluene
- Trichloroethane
- Trichloroethanol
- Trichloroethylene
- YM-31636
Antagonists: Antiemetics: AS-8112
- Alosetron
- Azasetron
- Batanopride
- Bemesetron
- Cilansetron
- Dazopride
- Dolasetron
- Galanolactone
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- Zacopride
- Zatosetron; Atypical antipsychotics: Clozapine
- Olanzapine
- Quetiapine; Tetracyclic antidepressants: Amoxapine
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- Mirtazapine; Others: CSP-2503
- ICS-205,930
- MDL-72,222
- Memantine
- Nitrous Oxide
- Ricasetron
- Sevoflurane
- Tedatioxetine
- Thujone
- Tropanserin
- Vortioxetine
- Xenon
|
|
5-HT4
|
- Agonists: Gastroprokinetic Agents: Cinitapride
- Cisapride
- Dazopride
- Metoclopramide
- Mosapride
- Prucalopride
- Renzapride
- Tegaserod
- Velusetrag
- Zacopride; Others: 5-MT
- BIMU8
- CJ-033,466
- PRX-03140
- RS-67333
- RS-67506
- SL65.0155
- Antagonists: GR-113,808
- GR-125,487
- L-Lysine
- Piboserod
- RS-39604
- RS-67532
- SB-203,186
- SB-204,070
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5-HT5A
|
- Agonists: Lysergamides: Ergotamine
- LSD; Tryptamines: 5-CT; Others: Valerenic Acid
Antagonists: Asenapine
- Latrepirdine
- Metitepine/Methiothepin
- Ritanserin
- SB-699,551
* Note that the 5-HT5B receptor is not functional in humans.
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5-HT6
|
- 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
|
|
5-HT7
|
- 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; Others: Butaclamol
- EGIS-12,233
- Ketanserin
- LY-215,840
- Metitepine/Methiothepin
- Pimozide
- 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
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Reuptake inhibitors
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SERT
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- Selective serotonin reuptake inhibitors (SSRIs): Alaproclate
- Citalopram
- Dapoxetine
- Desmethylcitalopram
- Desmethylsertraline
- Escitalopram
- Femoxetine
- Fluoxetine
- Fluvoxamine
- Indalpine
- Ifoxetine
- Litoxetine
- Lubazodone
- Omiloxetine
- Panuramine
- Paroxetine
- Pirandamine
- RTI-353
- Seproxetine
- Sertraline
- Vilazodone
- Vortioxetine
- Zimelidine; Serotonin-norepinephrine reuptake inhibitors (SNRIs): Bicifadine
- Desvenlafaxine
- Duloxetine
- Eclanamine
- Levomilnacipran
- Milnacipran
- Sibutramine
- Venlafaxine; Serotonin-norepinephrine-dopamine reuptake inhibitors (SNDRIs): Brasofensine
- Diclofensine
- DOV-102,677
- DOV-21,947
- DOV-216,303
- NS-2359
- SEP-225289
- SEP-227,162
- Tedatioxetine
- Tesofensine; Tricyclic antidepressants (TCAs): Amitriptyline
- Butriptyline
- Cianopramine
- Clomipramine
- Desipramine
- Dosulepin
- Doxepin
- Imipramine
- Lofepramine
- Nortriptyline
- Pipofezine
- Protriptyline
- Trimipramine; Tetracyclic antidepressants (TeCAs): Amoxapine; Piperazines: Nefazodone
- Trazodone; Antihistamines: Brompheniramine
- Chlorphenamine
- Diphenhydramine
- Mepyramine/Pyrilamine
- Pheniramine
- Tripelennamine; Opioids: Pethidine
- Methadone
- Propoxyphene; Others: Cocaine
- CP-39,332
- Cyclobenzaprine
- Dextromethorphan
- Dextrorphan
- EXP-561
- Fezolamine
- Mesembrine
- Nefopam
- PIM-35
- Pridefine
- Roxindole
- SB-649,915
- Tofenacin
- Ziprasidone
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VMAT
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- Ibogaine
- Reserpine
- Tetrabenazine
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Releasing agents
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- Aminoindanes: 5-IAI
- AMMI
- ETAI
- MDAI
- MDMAI
- MMAI
- TAI; Aminotetralins: 6-CAT
- 8-OH-DPAT
- MDAT
- MDMAT; Oxazolines: 4-Methylaminorex
- Aminorex
- Clominorex
- Fluminorex; Phenethylamines (also Amphetamines, Cathinones, Phentermines, etc): 2-Methyl-MDA
- 4-CAB
- 4-FA
- 4-FMA
- 4-HA
- 4-MTA
- 5-APDB
- 5-Methyl-MDA
- 6-APDB
- 6-Methyl-MDA
- AEMMA
- Amiflamine
- BDB
- BOH
- Brephedrone
- Butylone
- Chlorphentermine
- Cloforex
- Amfepramone
- Metamfepramone
- DCA
- DFMDA
- DMA
- DMMA
- EBDB
- EDMA
- Ethylone
- Etolorex
- Fenfluramine (Dexfenfluramine, Levofenfluramine)
- Flephedrone
- IAP
- IMP
- Iofetamine
- Lophophine
- MBDB
- MDA
- MDEA
- MDHMA
- MDMA
- MDMPEA
- MDOH
- MDPEA
- Mephedrone
- Methedrone
- Methylone
- MMA
- MMDA
- MMDMA
- MMMA
- NAP
- Norfenfluramine
- 4-TFMA
- pBA
- pCA
- pIA
- PMA
- PMEA
- PMMA
- TAP; Piperazines: 2C-B-BZP
- 3-MeOPP
- BZP
- DCPP
- MBZP
- mCPP
- MDBZP
- MeOPP
- Mepiprazole
- pCPP
- pFPP
- pTFMPP
- TFMPP; Tryptamines: 4-Methyl-αET
- 4-Methyl-αMT
- 5-CT
- 5-MeO-αET
- 5-MeO-αMT
- 5-MT
- αET
- αMT
- DMT
- Tryptamine (itself); Others: Indeloxazine
- Tramadol
- Viqualine
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Enzyme inhibitors
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Anabolism
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TPH
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AAAD
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- Benserazide
- Carbidopa
- Genistein
- Methyldopa
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Catabolism
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MAO
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- Nonselective: Benmoxin
- Caroxazone
- Echinopsidine
- Furazolidone
- Hydralazine
- Indantadol
- Iproclozide
- Iproniazid
- Isocarboxazid
- Isoniazid
- Linezolid
- Mebanazine
- Metfendrazine
- Nialamide
- Octamoxin
- Paraxazone
- Phenelzine
- Pheniprazine
- Phenoxypropazine
- Pivalylbenzhydrazine
- Procarbazine
- Safrazine
- Tranylcypromine; MAO-A Selective: Amiflamine
- Bazinaprine
- Befloxatone
- Befol
- Brofaromine
- Cimoxatone
- Clorgiline
- Esuprone
- Harmala alkaloids (Harmine
- Harmaline
- Tetrahydroharmine
- Harman
- Norharman, etc)
- Methylene Blue
- Metralindole
- Minaprine
- Moclobemide
- Pirlindole
- Sercloremine
- Tetrindole
- Toloxatone
- Tyrima
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Others
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Precursors
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Cofactors
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- Ferrous iron (Fe2+)
- Magnesium (Mg2+)
- Tetrahydrobiopterin
- Vitamin B3 (Niacin
- Nicotinamide → NADPH)
- Vitamin B6 (Pyridoxine
- Pyridoxamine
- Pyridoxal → Pyridoxal phosphate)
- Vitamin B9 (Folic Acid → Tetrahydrofolic acid)
- Vitamin C (Ascorbic acid)
- Zinc (Zn2+)
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Others
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- Activity enhancers: BPAP
- PPAP; Reuptake enhancers: Tianeptine
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