Norfluoxetine is an active N-desmethyl metabolite of the antidepressant fluoxetine that inhibits serotonin uptake. Norfluoxetine is selective serotonin reuptake inhibitor (SSRI) but little is known about its pharmacological actions. Seproxetine (S- Norfluoxetine) was being investigated by Eli Lilly as an antidepressant but development was never completed and the drug was never marketed.

(+)-DDMS (R-Didesmethylsibutramine , (R)-DDMS) is one of sibutramine active metabolites. Sibutramine is widely used in the treatment of obesity. Sibutramine acts by inhibiting the reuptake of serotonin and noradrenaline in synapses, thereby enhancing both satiety and energy expenditure. In preclinical models (R)-enantiomer of Didesmethylsibutramine was clearly more potent than the (S)-enantiomers and (R)-didesmethylsibutramine shows some activity in all tests. (S)-didesmethylsibutramine affected locomotor behavior and the Porsolt test but appeared to be completely inactive on food intake. R-Didesmethylsibutramine is more potent than sibutramine in depressing food intake and decreasing body weight, suggest that these enantioselective metabolites might be safer and more effective than sibutramine as potential therapies for obesity.

Guanadrel is a postganglionic adrenergic blocking agent. Uptake of guanadrel and storage in sympathetic neurons occurs via the norepinephrine pump or transporter. Guanadrel slowly displaces norepinephrine from its storage in nerve endings and thereby blocks the release of norepinephrine normally produced by nerve stimulation. The reduction in neurotransmitter release in response to sympathetic nerve stimulation, as a result of catecholamine depletion, leads to reduced arteriolar vasoconstriction, especially the reflex increase in sympathetic tone that occurs with a change in position. Guanadrel is used to treat and control hypertension.

Maprotiline is a tetracyclic antidepressant with similar pharmacological properties to tricyclic antidepressants (TCAs). Similar to TCAs, maprotiline inhibits neuronal norepinephrine reuptake, possesses some anticholinergic activity, and does not affect monoamine oxidase activity. It differs from TCAs in that it does not appear to block serotonin reuptake. Maprotiline may be used to treat depressive affective disorders, including dysthymic disorder (depressive neurosis) and major depressive disorder. Maprotiline is effective at reducing symptoms of anxiety associated with depression. The mechanism of action of maprotiline is not precisely known. It does not act primarily by stimulation of the central nervous system and is not a monoamine oxidase inhibitor. The postulated mechanism of maprotiline is that it acts primarily by potentiation of central adrenergic synapses by blocking reuptake of norepinephrine at nerve endings. This pharmacologic action is thought to be responsible for the drug’s antidepressant and anxiolytic effects. The mean time to peak is 12 hours. The half-life of elimination averages 51 hours.