Nortriptyline

Trade Name Manufacturer Country Year Introduced 

Chemical Name 3-(10,11-Dihydro-5H-dibenzo(a,d] cyclohepten-5-vlidene)-N-methyl-1-pro-panamlne 

Common Name Desmethylamitriptyline desitriptyline Structural Formula  

A mixture of 114.5 g of 5-(3-chloropropylidene)dlbenzo[a i] cyclohepta[1,4] diene, 75 ml of benzene, and about 400 ml of methylamine is heated in an autoclave at 120°Cfor six hours. The excess methylamine is distilled from the reaction mixture under vacuum and the residue is stirred with 300 ml of water. Acidification of the mixture with hydrochloric acid causes the separation of the hydrochloride of 5-(3-methylaminopropylidene)dlbenzo[a,dlcyclo-hepta[ 1,4] diene. The product is collected by filtration and is purified by recrystallizatlon from a mixture of absolute ethanol and ethyl acetate. MP 210°C to 212 C. 

Common Name Desmethylamitriptyllne desitrlptyllne Structural Formula  

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Desipramine [50-47-5] (35) and nortriptyline [72-69-5] (36) are demethylated derivatives and principal metaboHtes of (32) and (33), respectively. Both compounds possess less sedative and stronger psychomotor effects than the tertiary amine counterparts, probably because tricycHcs containing secondary amine groups generally show greater selectivity for inhibiting the reuptake of norepinephrine compared with the reuptake of serotonin. Protriptyline [438-60-8] (37), a stmctural isomer of nortriptyline, is another important secondary amine that displays a similar clinical profile. 

Antidepressants are used in the treatment of neuropathic pain and headache. They include the classic tricyclic compounds and are divided into nonselective nor-adrenaline/5-HT reuptake inhibitors (e.g., amitriptyline, imipramine, clomipramine, venlafaxine), preferential noradrenaline reuptake inhibitors (e.g., desipramine, nortriptyline) and selective 5-HT reuptake inhibitors (e.g., citalopram, paroxetine, fluoxetine). The reuptake block leads to a stimulation of endogenous monoaminer-gic pain inhibition in the spinal cord and brain. In addition, tricyclics have NMDA receptor antagonist, endogenous opioid enhancing, Na+ channel blocking, and K+ channel opening effects which can suppress peripheral and central sensitization. Block of cardiac ion channels by tricyclics can lead to life-threatening arrhythmias. The selective 5-HT transporter inhibitors have a different side effect profile and are safer in cases of overdose [3]. 

Older- tricyclic antidepressants are set in italics. The specificity of action of tricyclic antidepressants (in particular of amitritpyline, imipramine, doxepine, nortriptyline, duloxetine, maprotiline) is limited because at therapeutic levels these drugs also block recqDtors (Hrhistamine, aradrenergic, muscarinic). 

C20H23N 50-48-6) see Amitriptylinoxide Nortriptyline amitriptyline methiodide (CjjHjftlN 33445-20-4) see Nortriptyline ammonium carbonate... 

C jH 7Br 3436-04-2) see Amitriptyline Amitriptylinoxide Nortriptyline Al-(3-bromopropyl)phthalimide (C, H,oBrN02 5460-29-7) see Roxatidine acetate... 

Nortriptyline. Nortriptyhne, a tricychc antidepressant, has been shown in double-blind, placebo-controlled randomized trials to be superior to placebo for smoking cessation (Prochazka et al. 1998). Nortriptyline appears to have efficacy comparable to that of bupropion for smoking cessation (Hall et al. 2002). The efficacy of this agent may be improved with more intensive behavioral therapies (Hall et al. 1998). Nortriptyline s mechanism of action is thought to relate to its noradrenergic and serotonergic reuptake blockade, because these two neurotransmitters have been implicated in the neurobiology of nicotine dependence. Side effects of nortiptyline are typical of tricyclic antidepressants and include dry mouth, blurred vision, constipation, and orthostatic hypotension. Nortriptyline appears to have some utility for smokers with a past history of major depression, and it can be recommended as a second-... 

Hall SM, Reus VI, Munoz RF, et al Nortriptyline and cognitive-behavioral therapy in the treatment of cigarette smoking. Arch Gen Psychiatry 55 683-690, 1998 Hall SM, Humfleet GL, Reus VI, et al Psychological intervention and antidepressant treatment in smoking cessation. Arch Gen Psychiatry 59 930-936, 2002 Hayford KE, Patten CA, Rummans TA, et al Efficacy of bupropion for smoking cessation in smokers with a former history of major depression or alcoholism. Br J Psychiatry 174 173-178, 1999... 

Oncken CA, Hatsukami DK, Lupo VR, et al Effects of short-term use of nicotine gum in pregnant smokers. Clin Pharmacol Ther 59 654-61, 1996 Pomerleau OF, Pomerleau CS Neuroregulators and the reinforcement of smoking towards a biobehavioral explanation. Neurosci Biobehav Rev 8 503—513, 1984 Prochazka AV, Weaver MJ, Keller RT, et al A randomized trial of nortriptyline for smoking cessation. Arch Intern Med 158 2035-2039, 1998 Puska P, Korhonen HJ, Vartiainen E, et al Combined use of nicotine patch and gum compared with gum alone in smoking cessation a clinical trial in North Karelia. Tob Control 4 231-235, 1995... 

Note Derivatization with this reagent sequence in combination with extraction and TLC separation is speciftc for amitriptyline and nortriptyline in the analysis of plasma furthermore its high sensitivity allows its employment in pharmacokinetic studies, e. g. after the oral administration of a single dose of 25 mg amitriptyline. 

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