A serotonin reuptake inhibitor (SRI) is a type of drug that acts as a reuptake inhibitor for the neurotransmitter serotonin (5-hydroxytryptamine [5-HT]) by blocking the action of the serotonin transporter (SERT). This in turn leads to increased extracellular concentrations of serotonin and, therefore, an increase in serotonergic neurotransmission.
SRIs are not synonymous with selective serotonin reuptake inhibitors (SSRIs), as the latter term is usually used to describe the class of antidepressants of the same name, and, because SRIs, unlike SSRIs, can be either selective or nonselective in their action. For example, cocaine, which nonselectively inhibits the reuptake of serotonin, norepinephrine, and dopamine, can be called an SRI, but not an SSRI.
[edit] Indications
SRIs may be used in the clinical treatment of mood disorders such as major depressive disorder (MDD), dysthymia, and bipolar disorder (BD) as antidepressants, anxiety disorders such as generalized anxiety disorder (GAD), social phobia (SP) also known as social anxiety disorder (SAD), obsessive-compulsive disorder (OCD), and panic disorder (PD) as anxiolytics, post-traumatic stress disorder (PTSD), body dysmorphic disorder (BDD), eating disorders like anorexia nervosa and bulimia nervosa, and certain personality disorders such as borderline personality disorder (BPD), as well as chronic pain, neuralgia or neuropathic pain, and fibromyalgia as analgesics (see duloxetine, milnacipran, and bicifadine), irritable bowel syndrome (IBS) as gastroprokinetic agents, premature ejaculation (PE) (see dapoxetine), drug addiction as anticraving agents, and obesity for anorectic or weight loss purposes (see sibutramine).
[edit] Effects
[edit] General
SRIs can induce a wide range of psychological and physiological effects, including the following:
- Psychological
- A general and subjective alteration in consciousness
- Sedation or drowsiness
- Somnolence or sleepiness
- Fatigue or lethargy
- Malaise or lassitude
- Agitation or restlessness
- Akathisia or unpleasant sensations of "inner restlessness" and inability to sit still or remain motionless
- Decreased alertness, awareness, and wakefulness
- Impaired attention, focus, and concentration
- Decreased drive and motivation
- Cognitive and memory impairment
- Antidepressant benefits or mood lift
- Anxiolysis and/or stress reduction
- Apathy and/or anhedonia or emotional blunting
- Euphoria and/or dysphoria
- Antiaggressive or serenic effects, or even entactogen qualities
- Vivid, bizarre, or strange dreams, or a suppression of dreaming
- Psychedelia, consisting of mental imagery, auditory and visual hallucinations and distortions, and synesthesia
- Paradoxical exacerbation of depression and/or anxiety, as well as suicidal ideation, though usually only acute in nature
- Physiological
- Miscellaneous
It should be noted, however, that many of these effects are dependent on whether the administration of the SRI is acute or chronic. As an example, acute ingestion typically does not result in a mood lift, and chronic administration usually does not result in any sort of psychedelia whatsoever. Additionally, many of these properties are also dependent on whether the SRI in question is capable of crossing the blood-brain-barrier (BBB). Those that do not will only produce peripheral effects.
[edit] Overdose
At very high doses characterized by overdose, serotonin syndrome may develop, resulting in symptoms including the following:
- Psychological
- Physiological
- Miscellaneous
[edit] List of SRIs
- Pharmaceutical Drugs
- Dietary Supplements
- Street Drugs
- Research Chemicals
- Alaproclate (GEA-654)
- Bicifadine (DOV-220,075)
- Brasofensine (NS-2214)
- Bromantane (ADK-709)
- Diclofensine (Ro-8-4650)
- DOV-21,947
- DOV-102,677
- DOV-216,303
- Indatraline (Lu-19-005)
- Litoxetine (SL-810,385)
- Lubazodone (YM-992, YM-35,995)
- NS-2359 (GSK-372,475)
- SB-649,915
- SEP-225,289
- SEP-227,162
- Tametraline (CP-24,411)
- Tesofensine (NS-2330)
- Vilazodone (EMD-68,843)
- Viqualine (PK-5078)
[edit] See also
[edit] References
- ^ a b c Gillman PK. (2005). "Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity.". Br J Anaesth. 95 (4): 434–41. doi:10.1093/bja/aei210. PMID 16051647.
- ^ a b c d Yeh SY, Dersch C, Rothman R, Cadet JL (September 1999). "Effects of antihistamines on 3, 4-methylenedioxymethamphetamine-induced depletion of serotonin in rats". Synapse 33 (3): 207–17. doi:10.1002/(SICI)1098-2396(19990901)33:3<207::AID-SYN5>3.0.CO;2-8. PMID 10420168.
- ^ Werling LL, Keller A, Frank JG, Nuwayhid SJ (2007). "A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder". Exp Neurol. 207 (2): 248–57. doi:10.1016/j.expneurol.2007.06.013. PMID 17689532.
- ^ Pharmaceutical compositions containing mesembrine and related compounds. U.S. Patent 6,288,104 (PDF)
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- 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
- 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
- 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
- PRX-00023
- Robalzotan
- S-15535
- SB-649,915
- SDZ 216-525
- Spiperone
- Spiramide
- Spiroxatrine
- UH-301
- WAY-100,135
- WAY-100,635
- Xylamidine
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- 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
- CP-286,601
- GR-46611
- L-694,247
- L-772,405
- PNU-109,291
- PNU-142,633
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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- 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
- CP-809,101
- Dimemebfe
- Lorcaserin
- Medifoxamine
- 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
- Amoxapine
- Aptazapine
- Etoperidone
- Fluoxetine
- Mianserin
- Mirtazapine
- Nefazodone
- Nortriptyline
- Tedatioxetine
- Trazodone; Others: Adatanserin
- 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
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- 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
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- 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
- 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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Serotonin modulators and stimulators (SMSs)
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Others
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Nonselective
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MAOA-Selective
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MAOB-Selective
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