Serotonergic presynaptic nerve

Heteroreceptors (HRs), like autoreceptors, can either suppress (inhibitory autoreceptors such as the tt2-adrenergic) or enhance the release of neurotransmitters. They are termed heteroreceptors since they are activated by neurotransmitters (e.g. norepinephrine) different from those produced by the nerve on which they are located (e.g. serotonergic). There might be numerous different heteroreceptors that bind various neurotransmitters on a single nerve. Table 1.2 summarizes some of the main modulating mechanisms relevant to intact functioning of the presynaptic nerve. Psychotropic medications can either enhance or suppress many of the major processes or modulatory events listed in this chapter. - ... 

This is a 5-HT1 agonist (inhibiting the release of serotonin from presynaptic nerve terminals). Hence, even though it suppresses central serotonergic transmission (opposite to the effect of sertraline), there is an increased risk of central nervous system toxicity. Thus, the combined use of sertraline and sumatriptan is not usually recommended. 

Reuptake inhibitor An indirectly acting drug that increases the activity of transmitters in the synapse by inhibiting their reuptake into the presynaptic nerve ending. May act selectively on noradrenergic, serotonergic, or both types of nerve endings... 

A related strategy would be to inactivate the 5-HTib/id autoreceptors which are found on serotonergic nerve terminals and so prevent feedback inhibition of 5-HT release in the terminal field. These drugs would not prevent the impact of indirect activation of 5-HTia receptors, and the reduced neuronal firing, by SSRIs (described above), but they would augment 5-HT release in the terminal field once the presynaptic 5-HTia receptors have desensitised. Selective 5-HTib/id antagonists have been developed only recently but will doubtless soon be tested in humans. 

Hence, these studies in guinea pig suggest that, in addition to their presynaptic location on serotonergic nerve terminals where they act as 5-HT autoreceptors... 

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