Interactions of monoamines

There is now increasing evidence that drugs that affect one neurotransmitter system can also affect another through downstream effects. If one looks simply at serotonin, there are innumerable examples. Thus, serotonergic heteroceptors are found on neurons primarily involved in the release of other neurotransmitters; there is evidence that 5-HT1D receptors may act in an inhibitory manner in this way. Noradrenergic receptors may be present on serotonergic nerve cell bodies and terminals: a 1 -receptors on serotonergic cell bodies act to increase cell firing and 5-HT release, while a2-receptors are present on serotonergic nerve terminals and inhibit 5-HT release. Projections of serotonergic neurons to other areas of the brain are known to inhibit dopaminergic function in the cortex and elsewhere. The serotonin transporter protein is thought to interact with the ability of a2-receptors to inhibit 5-HT cell firing. Finally, noradrenaline reuptake inhibition is potentiated in the presence of simultaneous 5-HT reuptake inhibition.

It is likely that a number of neurotransmitter alterations are present in depression. Clinically, it is of relevance that drugs that act on both serotonin and noradrenaline, such as amitriptyline (Barbui & Hotopf, 2001) and venlafaxine (Smith et al., 2002), may have slightly enhanced efficacy in the treatment of depression.

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