nortriptyline brands

Molecular formula: C19H21N

Though prescribing information does not identify a specific mechanism of action for nortriptyline, is believed that nortriptyline either inhibits the reuptake of the neurotransmitter serotonin at the neuronal membrane or acts at the level of the beta-adrenergic receptors. It displays a more selective reuptake inhibition for noradrenaline, which may explain increased symptom improvement after nortriptyline therapy. Tricyclic antidepressants do not inhibit monoamine oxidase nor do they affect dopamine reuptake. As with other tricyclics, nortriptyline displays affinity for other receptors including mACh receptors, histamine receptors, 5-HT receptors, in addition to other receptors. The mechanism of adverse imipramine-induced reactions ... was investigated by precipitating such reactions in rats with three injections (ip) of imipramine (5-40 mg/kg) at 24, 5, and 1 hr before testing, and comparing their occurrence with comparable treatments using specific noradrenergic and serotonergic reuptake inhibitors (nortriptyline (10 or 30 mg/kg, ip), citalopram (0.5-5.0 mg/kg, ip)). This initial study indicated that these reactions were mediated by imipramine's noradrenergic effects. The effect of equal-dose regimens of amitriptyline and nortriptyline on the concn of serotonin, dopamine and major acidic metabolites was compared in 5 distinct brain regions as a function of inbred mouse strain. Amitriptyline incr to a greater extent the regional brain serotonin levels in the albino BALB/c mouse than did nortriptyline. Both drugs incr serotonin levels but decr cerebral 5-hydroxyindoleacetic acid levels in some distinct brain regions of the black C57BL/6 mouse strain. The results suggest a strain-dependent differential incr in brain serotonin turnover in specific mouse strain brain regions which may account for the greater incidence of amitriptyline-induced sedation and seizures. The BALB/c mouse was also found to be more sensitive than the C57BL/6 strain to the action of both drugs on dopamine and major acidic metabolites with amitriptyline showing more regional brain potency than nortriptyline. The data suggest an incr in dopamine turnover particularly in brain areas assoc with motor function and posture which may account for tricyclic antidepressant-induced extrapyramidal disorders. The results also indicate that the C57BL/6 mouse strain may be of experimental value for studying the mechanism underlying tricyclic-induced adverse reactions relevant to sedation and movement disorders as a function of genetic predisposition. Neuropathic pain is pain arising as a direct consequence of a lesion or disease affecting the somatosensory system. It is usually chronic and challenging to treat. Some antidepressants are first-line pharmacological treatments for neuropathic pain. The noradrenaline that is recruited by the action of the antidepressants on reuptake transporters has been proposed to act through beta2-adrenoceptors (beta2-ARs) to lead to the observed therapeutic effect. However, the complex downstream mechanism mediating this action remained to be identified. In this study, we demonstrate in a mouse model of neuropathic pain that an antidepressant's effect on neuropathic allodynia involves the peripheral nervous system and the inhibition of cytokine tumor necrosis factor a (TNFa) production. The antiallodynic action of nortriptyline is indeed lost after peripheral sympathectomy, but not after lesion of central descending noradrenergic pathways. More particularly, we report that antidepressant-recruited noradrenaline acts, within dorsal root ganglia, on beta2-ARs expressed by non-neuronal satellite cells. This stimulation of beta2-ARs decreases the neuropathy-induced production of membrane-bound TNFa, resulting in relief of neuropathic allodynia. This indirect anti-TNFa action was observed with the tricyclic antidepressant nortriptyline, the selective serotonin and noradrenaline reuptake inhibitor venlafaxine and the beta2-AR agonist terbutali

Source: PubChem (NCBI) · compound 4543