RESEARCH MONOGRAPH · KDC-MN-215
Maprotiline
Maprotiline (Ludiomil) is a tetracyclic antidepressant from Ciba-Geigy, approved in the US in 1980, that blocks the norepinephrine pump selectively while having very little effect on serotonin. That makes it pharmacologically distinct from the standard tricyclic antidepressants of its era, even though its side-effect profile (dry mouth, constipation, sedation) looks similar because it still blocks histamine and acetylcholine receptors as a side hobby. Its most notorious problem is seizure risk, which is the highest of any antidepressant and goes up sharply at high doses or with rapid titration. That alone has pushed it to the back of the prescribing line; few clinicians use it now when newer NRIs like atomoxetine are available. 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 Kodiac editorial, not peer-reviewed.
Tetracyclic norepinephrine reuptake inhibitor
A tetracyclic NRI with TCA-like side effects but selective noradrenergic action; significant seizure risk at high dose.
Abstract
Maprotiline (N-methyl-9,10-ethanoanthracene-9(10H)-propylamine; CAS 10262-69-8; molecular formula C20H23N; molecular weight 277.40) is a tetracyclic norepinephrine reuptake inhibitor developed at Ciba-Geigy and approved in the US in 1980 under the trade name Ludiomil. NET affinity is approximately 11 nM with very weak SERT activity (Ki greater than 1 microM), making the compound a selective NRI structurally classed with the tetracyclics owing to its bridged anthracene scaffold. Significant H1 (Ki approximately 2 nM) and muscarinic activity produces a side effect profile resembling tricyclic antidepressants: sedation, anticholinergic effects, weight gain. Plasma half-life is 21 to 52 hours, the longest of the antidepressant class, owing to the bridged scaffold's resistance to CYP metabolism. The compound carries the highest seizure risk of any commonly used antidepressant (approximately 0.4 percent at therapeutic doses, increasing sharply in overdose). The seizure risk and TCA-like adverse profile have led to declining use in favor of mirtazapine and SSRIs.
Mechanism of action
Selective NET inhibition with significant H1 and muscarinic antagonism. Highest seizure risk among antidepressants.
Reported research dose ranges
Reported research dose ranges in the literature.
References
- Pinder RM, et al. Maprotiline: a review of its pharmacological properties and therapeutic efficacy in mental depressive states. Drugs 1977.
- Park J, Beck JR. Therapeutic and adverse effects of maprotiline. Hosp Formul 1986.
- Yamashita H, et al. Seizures during long-term maprotiline therapy. J Clin Psychiatry 1986.
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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.