ATC Group: N06AA Non-selective monoamine reuptake inhibitors

Amitriptyline is a tricyclic antidepressant and an analgesic. It prevents the re-uptake, and hence the inactivation of noradrenaline and serotonin at nerve terminals. Reuptake prevention of these monoamine neurotransmitters potentiate their action in the brain. This appears to be associated with the antidepressant activity.

Amoxapine is an antidepressant with a mild sedative component to its action. The mechanism of its clinical action in man is not well understood. Amoxapine is used in the treatment of major depressive disorder.

The therapeutic activity of clomipramine is believed to be based on its ability to inhibit the neuronal re-uptake of noradrenaline (NA) and serotonin (5-HT) released in the synaptic cleft, with inhibition of 5-HT reuptake being the more important of these activities.

Desipramine is a tricyclic antidepressant. Desipramine is not a monoamine oxidase inhibitor (MAOI) and does not act primarily as a central nervous system stimulant. It has been found in some studies to have a more rapid onset of action than imipramine.

Dosulepin is a tricyclic antidepressant which acts by inhibiting the re-uptake of monoamine neurotransmitters into presynaptic neurone at central nervous system, so producing a clinical antidepressant effect. Dosulepin, in common with other tricyclics, inhibits the reuptake of noradrenaline and 5-hydroxytryptamine, with a significantly greater action on the uptake of noradrenaline.

Doxepin is not a central nervous system stimulant nor a monoamine oxidase inhibitor. The current hypothesis is that the clinical effects are due, at least in part, to influences on the adrenergic activity at the synapses so that deactivation of noradrenaline by reuptake into the nerve terminals is prevented.

Imipramine is a tricyclic antidepressant and has several pharmacological actions including alpha-adrenolytic, antihistamine, anticholinergic and 5HT-receptor blocking properties. However, the main therapeutic activity is believed to be inhibition of the neuronal re-uptake of noradrenaline and 5HT. Imipramine is a so-called “mixed” re-uptake blocker, i.e. it inhibits the reuptake of NA and 5HT to about the same extent.

Lofepramine is a tricyclic antidepressant. It exerts its therapeutic effect by blocking the uptake of noradrenaline by the nerve cell thus increasing the amine in the synaptic cleft and hence the effect on the receptors.

Maprotiline is a tetracyclic antidepressant, psychoanaleptics, non-selective mono-amine reuptake inhibitor, which shares a number of basic therapeutic properties with the tricyclic antidepressants. It displays a well-balanced spectrum of action, brightening mood and alleviating anxiety, agitation and psychomotor retardation. In masked depression, it can exert a favourable influence on somatic symptoms.

Melitracen is a tricyclic antidepressant with activating properties in low doses. It has similar pharmacological properties as amitriptyline but is less sedative.

Nortriptyline is a tricyclic antidepressant with actions and uses similar to these of amitriptyline. It is the principal active metabolite of amitriptyline.

Opipramol has high affinity for the sigma binding sites (type 1 and type 2) and has an antagonistic effect at the type 1 histamine receptors. The affinity for the type 2A serotonin receptors, type 2 dopamine receptors and the α-adrenergic receptors is lower. In contrast to the structurally related tricyclic antidepressants, opipramol has only slight anticholinergic activity and does not inhibit the reuptake of serotonin or noradrenaline. In humans, opipramol has sedating, anxiolytic and slight mood-elevating effects.