Nortriptyline hydrochloride, the N-demethylated active metabolite of amitriptyline, is a dibenzocycloheptene-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, nortriptyline does not affect mood or arousal, but may cause sedation. In depressed individuals, nortriptyline exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Secondary amine TCAs, such as nortriptyline, are more potent inhibitors of norepinephrine reuptake than tertiary amine TCAs, such as amitriptyline. TCAs also down-regulate cerebral cortical β-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine-H1 receptors, α1-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. See toxicity section below for a complete listing of side effects. Nortriptyline exerts less anticholinergic and sedative side effects compared to the tertiary amine TCAs, amitriptyline and clomipramine. Nortriptyline may be used to treat depression, chronic pain (unlabeled use), irritable bowel syndrome (unlabeled use), diabetic neuropathy (unlabeled use), post-traumatic stress disorder (unlabeled use), and for migraine prophylaxis (unlabeled use).
Indication
For the treatment of depression, chronic pain, irritable bowel syndrome, sleep disorders, diabetic neuropathy, agitation and insomnia, and migraine prophylaxis.
Pharmacology
Similar to protriptyline, nortriptyline is a tricyclic antidepressant of the dibenzocycloheptene type and is the active metabolite of amitriptyline.
Toxicity
Symptoms of overdose include cardiac dysrhythmias, severe hypotension, shock, congestive heart failure, pulmonary edema, convulsions, and CNS depression, including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic antidepressant toxicity. Side effects include: sedation, hypotension, blurred vision, dry mouth, constipation, urinary retention, postural hypotension, tachycardia, hypertension, ECG changes, heart failure, impaired memory and delirium, and precipitation of hypomanic or manic episodes in bipolar depression. Withdrawal symptoms include gastrointestinal disturbances, anxiety, and insomnia.
Affected Organisms
Humans and other mammals
Biotransformation
Undergoes hepatic metabolism via the same pathway as other TCAs.
Absorption
Well absorbed from the GI tract. Peak plasma concentrations occur 7-8.5 hours following oral administration.
Half Life
16 to 90+ hours
Protein Binding
Highly protein-bound in plasma and tissues.
Elimination
Approximately one-third of a single orally administered dose is excreted in urine within 24 hours. Small amounts are excreted in feces via biliary elimination.
References
•
Prochazka AV, Weaver MJ, Keller RT, Fryer GE, Licari PA, Lofaso D: A randomized trial of nortriptyline for smoking cessation. Arch Intern Med. 1998 Oct 12;158(18):2035-9.
[Pubmed]
An organic tricyclic compound that is 10,11-dihydro-5H-dibenzo[a,d][7]annulene substituted by a 3-(methylamino)propylidene group at position 5. It is an active metabolite of amitriptyline.
参考文献
PubChem文献
数据源提供
• Prochazka AV, Weaver MJ, Keller RT, Fryer GE, Licari PA, Lofaso D: A randomized trial of nortriptyline for smoking cessation. Arch Intern Med. 1998 Oct 12;158(18):2035-9. Pubmed
