Serotonin reuptake inhibitor



A serotonin reuptake inhibitor (SRI) is a type of drug which 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 each be called an SRI, but not an SSRI.

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).

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
 * Dizziness, lightheadedness, or vertigo
 * Blurry vision and/or nystagmus or involuntary and rapid eye movements
 * Mydriasis or pupil dilation
 * Xerostomia or dry mouth
 * Nausea and/or emesis or vomiting
 * Gastrointestinal disturbances such as diarrhea and/or constipation
 * Headache or migraine
 * Photosensitivity or increased risk of sunburn
 * Trismus or jaw clenching and/or bruxism or teeth grinding
 * Trembling, shakiness, or muscle temors
 * Restless legs syndrome (RLS)
 * Antidiuretic effects and/or ischuria or urinary retention or difficulting urinating
 * Sexual dysfunction, consisting of diminished libido, soft erections or erectile dysfunction, and anorgasmia or inability to ejaculate
 * Anorexia or decreased appetite and subsequent weight loss
 * Insomnia or inability to fall asleep
 * Analgesia or pain relief
 * Hypertension or increased blood pressure
 * Tachycardia or increased heart rate
 * Hyperthermia or increased body temperature
 * Hyperhidrosis or increased perspiration or sweating
 * Autonomic dysfunction such as orthostatic hypotension
 * Hyponatremia or a water-electrolyte imbalance
 * Liver or kidney dysfunction, toxicity, or failure


 * Miscellaneous
 * Decreased drug cravings and/or addiction
 * Drug tolerance with time and/or chronic administration, potentially resulting in dependence
 * Drug interactions such as abolished effects from serotonin releasing agents (SRAs) like MDMA ("Ecstasy")

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.

Overdose
At very high doses characterized by overdose, serotonin syndrome may develop, resulting in symptoms including the following:


 * Psychological
 * Disorientation and/or confusion
 * Anxiety, paranoia, and/or panic attacks
 * Hypervigilance or increased sensitivity to perceptual stimuli, accompanied by significantly increased threat detection
 * Hypomania or full-blown mania
 * Derealization and/or depersonalization
 * Hallucinations and/or perceptual disturbances


 * Physiological
 * Myoclonus or involuntary and intense muscle twitching
 * Hyperreflexia or overresponsive or overreactive reflexes
 * Tachypnoea or rapid breathing
 * Chest pain and/or pulmonary hypertension (PH)
 * Severe hyperthermia, potentially resulting in organ failure


 * Miscellaneous
 * Syncope or fainting or loss of consciousness
 * Seizures or convulsions
 * Organ failure (as mentioned above)
 * Neurotoxicity or brain damage
 * Coma and/or death

List of SRIs

 * Pharmaceutical Drugs


 * Selective Serotonin Reuptake Inhibitors (SSRIs)
 * Citalopram (Celexa)
 * Dapoxetine (Priligy)
 * Escitalopram (Lexapro, Cipralex)
 * Femoxetine (Malexil)
 * Fluoxetine (Prozac)
 * Fluvoxamine (Luvox)
 * Indalpine (Upstene)
 * Paroxetine (Paxil, Seroxat)
 * Sertraline (Zoloft, Lustral)
 * Zimelidine (Normud, Zelmid)


 * Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)
 * Desvenlafaxine (Pristiq)
 * Duloxetine (Cymbalta)
 * Milnacipran (Ixel, Savella)
 * Venlafaxine (Effexor)


 * Tricyclic Antidepressants (TCAs)
 * Amitriptyline (Elavil)
 * Butriptyline (Evadyne)
 * Clomipramine (Anafranil)
 * Dibenzepin (Noveril)
 * Dosulepin (Prothiade)
 * Doxepin (Adapin, Sinequan)
 * Imipramine (Tofranil)
 * Lofepramine (Lomont, Gamanil)
 * Nortriptyline (Pamelor, Aventyl)
 * Protriptyline (Vivactil)
 * Trimipramine (Surmontil)


 * Tetracyclic Antidepressants (TeCAs)
 * Amoxapine (Asendin)


 * Opioid Analgesics
 * Meperidine/Pethidine (Demerol)
 * Methadone (Dolophine, Methadose)
 * Propoxyphene (Darvon)


 * First-Generation Antihistamines
 * Chlorpheniramine (Chlor-Trimeton, etc.)
 * Diphenhydramine (Benadryl, etc.)
 * Mepyramine/Pyrilamine (Anthisan, etc.)
 * Tripelennamine (Pyribenzamine, etc.)


 * Miscellaneous Agents
 * Cyclobenzaprine (Flexeril)
 * Dextromethorphan (DXM; Robitussin, etc.)
 * Dextrorphanol (DXO) (an active metabolite of DXM)
 * Nefazodone (Serzone)
 * Nefopam (Acupan)
 * Sibutramine (Meridia, Reductil)
 * Trazodone (Desyrel)
 * Ziprasidone (Geodon, Zeldox)


 * Dietary Supplements
 * Adhyperforin (found in Hypericum perforatum (St. John's Wort))
 * Hyperforin (found in Hypericum perforatum (St. John's Wort))
 * Mesembrine (found in Sceletium tortuosum (Kanna))


 * Street Drugs
 * Cocaine (found in Erythroxylum coca (Coca))


 * 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)