Nortriptyline
Secondary-amine tricyclic antidepressant (NET-preferring), Rx for depression and neuropathic pain.
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Pharmacology
Contents
WHAT IS NORTRIPTYLINE?
Detailed overview
Nortriptyline is a secondary-amine tricyclic antidepressant (TCA) and the active metabolite of amitriptyline, in clinical use since the 1960s. It works mainly by blocking the norepinephrine transporter (NET), with weaker serotonin reuptake inhibition, while also antagonizing histamine H1, muscarinic and alpha-1 adrenergic receptors, which drives most of its side effects. Beyond major depression it is widely used off-label for neuropathic pain, chronic tension-type headache and migraine prophylaxis, and as a second-line smoking-cessation aid. It has a comparatively narrow therapeutic window and a well-defined target plasma range (roughly 50 to 150 ng/mL), so it is a prescription drug that requires medical supervision and can be dangerous in overdose.
Mechanism
NET-preferring reuptake inhibitor (TCA)
Half-life
~18-44 hours (about a day)
Legal status
Prescription antidepressant (Rx)
Receptor profile
- Norepinephrine transporter (NET)Strong
- Serotonin transporter (SERT)Moderate
- Histamine H1 receptorModerate
- Muscarinic acetylcholine receptorModerate
- Alpha-1 adrenergic receptorModerate
Safety
Side effects, stop signs, contraindications
Side effects · 6
- Anticholinergic effects: dry mouth, constipation, blurred vision, urinary retention
- Drowsiness, sedation and weight gain (H1 antagonism)
- Orthostatic hypotension and dizziness (alpha-1 blockade)
- Cardiac effects: tachycardia, arrhythmia, QT changes; dangerous in overdose
- Sexual dysfunction, sweating, tremor
- Increased risk of suicidal ideation in people under 25 (class-wide warning)
Contraindications · 5
- Recent myocardial infarction, significant heart disease or conduction defects
- Concurrent or recent (within 14 days) MAO inhibitor use
- Known hypersensitivity to tricyclic antidepressants
- Caution or avoidance in mania and bipolar disorder (can trigger a switch), narrow-angle glaucoma, urinary retention and seizure disorders
- Pregnancy and breastfeeding: only if clearly indicated, under medical advice
Related Nootropics
Same therapeutic category
Studies
Related research and clinical findings
Nortriptyline and interpersonal psychotherapy as maintenance therapies for recurrent major depression: a randomized controlled trial in patients older than 59 years
Reynolds CF 3rd, Frank E, Perel JM, Imber SD, Cornes C, Miller MD, et al.
Nortriptyline for neuropathic pain in adults
Derry S, Wiffen PJ, Aldington D, Moore RA
Quantitative analysis of nortriptyline's analgesic properties: a comparative systematic review and meta-analysis
Efficacy and safety of cytisine versus nortriptyline for smoking cessation: A multicentre, randomized, double-blinded and placebo-controlled trial
Antidepressants for smoking cessation
FAQ
FAQ
Secondary-amine tricyclic antidepressant (NET-preferring), Rx for depression and neuropathic pain.
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Structure & chemistry
The information here is strictly for educational and scientific purposes. It does not replace medical advice or clinical consultation, and it does not encourage illegal substance or pharmaceutical use. Data is sourced. When in doubt, consult your doctor.