Norepinephrine Reuptake Inhibitor Information
A norepinephrine reuptake inhibitor (NRI, NERI) or adrenergic reuptake inhibitor (ARI), is a type of drug that acts as a reuptake inhibitor for the neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline) by blocking the action of the norepinephrine transporter (NET). This in turn leads to increased extracellular concentrations of norepinephrine and epinephrine and therefore an increase in adrenergic neurotransmission.
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Indications
NRIs may be used in the clinical treatment of attention-deficit hyperactivity disorder (ADHD), narcolepsy, and fatigue or lethargy as stimulants, obesity as anorectics or appetite suppressants for weight loss purposes, as well as mood disorders such as major depressive disorder (MDD) as antidepressants, nasal or sinus congestion as decongestants, nocturnal enuresis or "bedwetting", hypotension and/or orthostatic hypotension as vasopressors, and both as augmentations and to offset some of the side effects of certain other drugs like the selective serotonin reuptake inhibitors (SSRIs) such as sexual dysfunction.
Effects
General
NRIs can induce a wide range of psychological and physiological effects, including the following:
- Psychological
- A general and subjective alteration in consciousness
- Stimulation, arousal, and hyperactivity
- Increased alertness, awareness, and wakefulness
- Increased energy and endurance
- Agitation or restlessness
- Enhanced attention, focus, and concentration
- Increased desire, drive, and motivation
- Improved cognition, memory, and learning
- Antidepressant benefits or mood lift
- Irritability, aggression, anger and/or rage
- Anxiety, negativity, paranoia, and/or panic attacks
- Malaise or lassitude
- Aphrodisiac effects
- Physiological
- Dizziness, lightheadedness, or vertigo
- Mydriasis or pupil dilation
- Xerostomia or dry mouth
- Nasal and/or sinus decongestion
- Nausea and/or emesis or vomiting
- Gastrointestinal disturbances
- Headache or migraine
- Trembling, shakiness, or muscle tremors
- Diuretic effects or increased or frequent urination
- 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
- Miscellaneous
- Drug tolerance with time and/or chronic administration, potentially resulting in dependence
- Drug interactions such as abolished effects from norepinephrine releasing agents like ephedrine
It should be noted, however, that many of these properties are dependent on whether the NRI in question is capable of crossing the blood-brain-barrier (BBB). Those that do not will produce only peripheral effects.
Overdose
At very high doses characterized by overdose, a number of symptoms may come to prominence, as well as hypertensive crisis, including the following:
- Psychological
- Disorientation and/or confusion
- Severe anxiety, paranoia, and/or panic attacks
- Hypervigilance or increased sensitivity to perceptual stimuli, accompanied by significantly increased threat detection
- Physiological
- Myoclonus or involuntary and intense muscle twitching
- Hyperreflexia or overresponsive or overreactive reflexes
- Tachypnoea or rapid breathing and/or dyspnea or shortness of breath
- Palpitations or abnormal awareness of the beating of the heart
- Angina pectoris or severe chest pain
- Cardiac arrhythmia or abnormal electical activity of the heart
- Circulatory shock or cardiogenic shock
- Vasculitis or destruction of blood vessels
- Cardiotoxicity or damage to the heart
- Cardiac arrest, myocardial infarction or heart attack, and/or heart failure
- Hemorrhage and/or stroke
- Miscellaneous
- Syncope or fainting or loss of consciousness
- Seizures or convulsions
- Neurotoxicity or brain damage
- Coma and/or death
Abuse
In contrast to dopamine reuptake inhibitors (DRIs) such as cocaine and methylphenidate, NRIs without DRI properties that do not affect dopamine are incapable of inducing significant rewarding effects and are not self-administered in rodents, and, as a result, they have a negligible abuse potential in comparison.[1][2]
List of NRIs
- Pharmaceutical Drugs
- Selective Norepinephrine Reuptake Inhibitors (NRIs)
- Atomoxetine/Tomoxetine (Strattera)
- Mazindol (Mazanor, Sanorex)
- Reboxetine (Edronax, Vestra)
- Viloxazine (Vivalan)
- Norepinephrine-Dopamine Reuptake Inhibitors (NDRIs)
- Amineptine (Survector, Maneon, Directin)
- Bupropion (Wellbutrin, Zyban)
- Dexmethylphenidate (Focalin)
- Fencamfamine (Glucoenergan, Reactivan)
- Fencamine (Altimina, Sicoclor)
- Lefetamine (Santenol)
- Methylphenidate (Ritalin, Concerta, Metadate, Methylin)
- Pipradrol (Meretran)
- Prolintane (Promotil, Katovit)
- Pyrovalerone (Centroton, Thymergix)
- Difemetorex
- Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)
- Desvenlafaxine (Pristiq)
- Duloxetine (Cymbalta)
- Milnacipran (Ixel, Savella)
- Venlafaxine (Effexor)
- Tricyclic Antidepressants (TCAs)
- Amitriptyline (Elavil)
- Butriptyline (Evadyne)
- Clomipramine (Anafranil)
- Desipramine (Norpramin, Pertofrane)
- Dosulepin (Prothiade)
- Doxepin (Adapin, Sinequan)
- Imipramine (Tofranil)
- Lofepramine (Lomont, Gamanil)
- Nortriptyline (Pamelor, Aventyl)
- Protriptyline (Vivactil)
- Trimipramine (Surmontil)
- Tetracyclic Antidepressants (TeCAs)
- Amoxapine (Asendin)
- Maprotiline (Ludiomil)
- Mianserin (Bolvidon, Norval, Tolvon)
- Miscellaneous Agents
- Cyclobenzaprine (Flexeril)
- Mesocarb (Sidnocarb, Sydnocarb)
- Nefazodone (Serzone) (weak)
- Nefopam (Acupan)
- Sibutramine (Meridia, Reductil)
- Tapentadol (Nucynta)
- Tramadol (Tramal, Ultram)
- Ziprasidone (Geodon, Zeldox)
- Ginkgo biloba [3]
- Adhyperforin (found in Hypericum perforatum (St. John's Wort))
- Hyperforin (found in Hypericum perforatum (St. John's Wort))
- Street Drugs
- Cocaine (found in Erythroxylum coca (Coca))
- Desoxypipradrol (2-DPMP)
- Diphenylprolinol (D2PM)
- Methylenedioxypyrovalerone (MDPV)
- Selective Norepinephrine Reuptake Inhibitors (NRIs)
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- Ciclazindol (Wy-23,409)
- Esreboxetine
- Manifaxine (GW-320,659)
- Nisoxetine (LY-94,939)
- Radafaxine (GW-353,162)
- Tandamine (AY-23,946)
- WYE-103231[4]
- [5]
- 1-(Indolin-1-yl)-1-phenyl-3-propan-2-olamines[6]
- 1- or 3-(3-Amino-2-hydroxy-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones[7]
- (+)-S-21, thienyl-based[8]
- Serotonin-Norepinephrine-Dopamine Reuptake Inhibitors (SNDRIs)
- Bicifadine (DOV-220,075)
- Brasofensine (NS-2214)
- Diclofensine (Ro-8-4650)
- DOV-21,947
- DOV-102,677
- DOV-216,303
- Indatraline (Lu-19-005)
- NS-2359 (GSK-372,475)
- Oxaprotiline (CGP-12,103-A)
- SEP-225,289
- SEP-227,162
- Tesofensine (NS-2330)
See also
- Adrenergic
- Reuptake inhibitor
- Serotonin reuptake inhibitor (SRI)
- Selective serotonin reuptake inhibitor (SSRI)
- Serotonin-norepinephrine reuptake inhibitor (SNRI)
- Dopamine reuptake inhibitor (DRI)
- Norepinephrine-dopamine reuptake inhibitor (NDRI)
- Serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI)
References
- ^ Wee S, Woolverton WL (September 2004). "Evaluation of the reinforcing effects of atomoxetine in monkeys: comparison to methylphenidate and desipramine". Drug and Alcohol Dependence 75 (3): 271–6. doi:10.1016/j.drugalcdep.2004.03.010. PMID 15283948.
- ^ Gasior M, Bergman J, Kallman MJ, Paronis CA (April 2005). "Evaluation of the reinforcing effects of monoamine reuptake inhibitors under a concurrent schedule of food and i.v. drug delivery in rhesus monkeys". Neuropsychopharmacology 30 (4): 758–64. doi:10.1038/sj.npp.1300593. PMID 15526000.
- ^ Fehske, CJ; Leuner, K; Müller, WE (2009). "Ginkgo biloba extract (EGb761) influences monoaminergic neurotransmission via inhibition of NE uptake, but not MAO activity after chronic treatment". Pharmacological research : the official journal of the Italian Pharmacological Society 60 (1): 68–73. doi:10.1016/j.phrs.2009.02.012. PMID 19427589.
- ^ O'Neill, DJ; Adedoyin, A; Alfinito, PD; Bray, JA; Cosmi, S; Deecher, DC; Fensome, A; Harrison, J et al (2010). "Discovery of novel selective norepinephrine reuptake inhibitors: 4-3-aryl-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl-1-(methylamino)butan-2-ols (WYE-103231)". Journal of medicinal chemistry 53 (11): 4511–21. doi:10.1021/jm100053t. PMID 20462211.
- ^ Fensome, A; Goldberg, J; McComas, CC; Trybulski, EJ; Woodworth, RP; Deecher, DC; Whiteside, GT; Zhang, P (2010). "Structure-activity relationships of norepinephrine reuptake inhibitors with benzothiadiazine dioxide or dihydrosulfostyril cores". Bioorganic & medicinal chemistry letters 20 (5): 1555–8. doi:10.1016/j.bmcl.2010.01.056. PMID 20153188.
- ^ Vu, AT; Cohn, ST; Zhang, P; Kim, CY; Mahaney, PE; Bray, JA; Johnston, GH; Koury, EJ et al (2010). "1-(Indolin-1-yl)-1-phenyl-3-propan-2-olamines as potent and selective norepinephrine reuptake inhibitors". Journal of medicinal chemistry 53 (5): 2051–62. doi:10.1021/jm901559e. PMID 20131864.
- ^ Zhang, P; Terefenko, EA; Bray, J; Deecher, D; Fensome, A; Harrison, J; Kim, C; Koury, E et al (2009). "1- or 3-(3-Amino-2-hydroxy-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones: Potent, selective, and orally efficacious norepinephrine reuptake inhibitors". Journal of medicinal chemistry 52 (18): 5703–11. doi:10.1021/jm900888c. PMID 19722525.
- ^ Sabatucci, JP; Mahaney, PE; Leiter, J; Johnston, G; Burroughs, K; Cosmi, S; Zhang, Y; Ho, D et al (2010). "Heterocyclic cycloalkanol ethylamines as norepinephrine reuptake inhibitors". Bioorganic & medicinal chemistry letters 20 (9): 2809–12. doi:10.1016/j.bmcl.2010.03.059. PMID 20378347.
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Categories:
- Drugs acting on the nervous system
- Norepinephrine reuptake inhibitors
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