Nortriptyline Hydrochloride

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Cat Number

API0232115

CAS Number

894-71-3

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Product Detail Description Scientific Support Customer Q&A

CAS Number

894-71-3

EINECS

212-973-0

Storage

Store at room temperature

Synonyms

Nortriptyline Hcl; Aventyl hydrochloride; DTXSID2045109; NSC-169453; 00FN6IH15D; DTXCID0025109

Molecular Formula

C19H22ClN

Molecular Weight

299.8

Smiles

CNCCC=C1C2=CC=CC=C2CCC3=CC=CC=C31.Cl

Appearance

White to off-white powder

Melting Point

217-220°C

Boiling Point

403.4°C at 760 mmHg

Relative Density

1.084

General Description

Nortriptyline hydrochloride is a secondary amine tricyclic antidepressant derived from amitriptyline by demethylation of the side-chain nitrogen. The molecule retains the dibenzocycloheptadiene ring system but has a single methyl group on the terminal amine. The hydrochloride salt improves aqueous solubility. Structurally, it is the N-desmethyl metabolite of amitriptyline and exhibits more selective norepinephrine reuptake inhibition than its parent compound.

Mechanism of Action

Nortriptyline potently inhibits the presynaptic reuptake of norepinephrine and, to a lesser extent, serotonin, increasing their concentrations in the synaptic cleft. It has minimal direct effects on dopamine reuptake. The drug also blocks histamine H1 receptors (causing sedation), muscarinic acetylcholine receptors (causing anticholinergic effects), and alpha-1 adrenergic receptors (causing orthostatic hypotension). Its secondary amine structure results in less sedative and anticholinergic burden compared to amitriptyline.

Application

Nortriptyline is indicated for the treatment of major depressive disorder and is also used off-label for neuropathic pain (e.g., diabetic neuropathy, postherpetic neuralgia), chronic tension-type headache, and migraine prophylaxis. It is sometimes preferred over other tricyclics in elderly patients due to its more favorable side effect profile. The drug is also used for smoking cessation as second-line therapy and for management of attention-deficit/hyperactivity disorder.

Using whole‑cell patch clamp in freshly isolated rabbit coronary arterial smooth muscle cells, nortriptyline inhibited voltage‑dependent K⁺ (Kv) currents in a concentration‑dependent manner (IC₅₀ 2.86 µM). The drug shifted the inactivation curve to more negative potentials without affecting the activation curve, and inhibition was not use‑dependent. Pre‑incubation with selective Kv1.5 or Kv2.1/2.2 inhibitors did not alter nortriptyline’s effect. The authors conclude that nortriptyline inhibits Kv channels in a concentration‑dependent and state‑independent manner, independent of serotonin reuptake.

Fig. 1 Effects of nortriptyline on voltage-dependent K+ (Kv) channel currents. (Shin SE, et al., 2017)

References

Shin SE, et al. Nortriptyline, a tricyclic antidepressant, inhibits voltage-dependent K+ channels in coronary arterial smooth muscle cells. Korean J Physiol Pharmacol. 2017;21(2):225-232.

Does Nortriptyline Hydrochloride discolor upon prolonged light exposure?

Yes, it is photosensitive and may darken over time. Store in light-resistant, tightly sealed containers, preferably amber glass, to prevent photodegradation.

What is the recommended storage temperature for Nortriptyline Hydrochloride?

Store at controlled room temperature (15-25°C). Avoid excessive heat above 30°C, which can accelerate formation of the dibenzocycloheptene-related impurities.

Is Nortriptyline Hydrochloride stable in solution for injectable or oral use?

Aqueous solutions are stable when protected from light and stored at room temperature for up to 24 hours.

How is the impurity nortriptyline N-oxide (an oxidative metabolite) monitored?

This degradation product is specifically quantified using a stability-indicating HPLC method with UV or electrochemical detection, ensuring it remains within USP limits.