RESEARCH MONOGRAPH · KDC-MN-219
Desipramine
Desipramine (Norpramin) is the active leftover of imipramine, FDA-approved in 1964, and the most norepinephrine-selective tricyclic antidepressant ever brought to market. The shift in selectivity comes from removing one methyl group from imipramine. The strongly noradrenergic profile makes it one of the more activating tricyclics and useful in attention deficit research, although it never gained an ADHD label. Compared to its parent it has lower anticholinergic and antihistamine burden, so it is somewhat better tolerated, but it shares the cardiac conduction problems of the whole tricyclic class and overdose is dangerous. Used in treatment-resistant depression and some neuropathic pain protocols. Not stocked by Kodiac. This monograph is provided for research and educational reference.
Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.
Tricyclic antidepressant (secondary amine)
The N-desmethyl active metabolite of imipramine; the most NET-selective TCA in clinical use.
Abstract
Desipramine (3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N-methylpropan-1-amine; CAS 50-47-5; molecular formula C18H22N2; molecular weight 266.38) is the N-desmethyl active metabolite of imipramine, approved by the FDA in 1964 under the trade name Norpramin. The compound is the most NET-selective TCA in clinical use (NET Ki approximately 0.83 nM, SERT Ki approximately 17 nM, ratio approximately 20). Off-target activity is reduced compared to imipramine: muscarinic (M1 Ki approximately 200 nM), H1 (Ki approximately 60 nM), and alpha-1 (Ki approximately 100 nM) antagonism are all weaker than the parent compound, producing a cleaner profile though still TCA-like. Plasma half-life is 15 to 24 hours; metabolism is via CYP2D6 and CYP2E1. Approved for major depressive disorder; used at higher doses (150 to 300 mg) for moderate-severe depression, at lower doses for ADHD (off-label) and neuropathic pain. Sodium channel block and consequent cardiotoxicity in overdose remain limitations. Used as the canonical NET-selective TCA in mechanism studies and as a reference compound for noradrenergic pharmacology.
Mechanism of action
Most NET-selective TCA; reduced anticholinergic and antihistaminergic burden compared to imipramine. Active metabolite of imipramine.
Reported research dose ranges
Reported research dose ranges in the literature.
References
- Tatsumi M, et al. Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol 1997.
- Reimherr FW, et al. Desipramine for adult attention deficit disorder. Am J Psychiatry 1995.
- Goldstein DJ. Long-term treatment of depression with desipramine and imipramine. Br J Clin Pharmacol 1991.
Read the full monograph
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The full reference document is provided strictly for research use only. It reports research dose ranges from the published literature, not instructions for use in humans or animals.
FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.