The release of neurotransmitters is modulated through presynaptic autoreceptors that are acted upon by the neurone's own transmitter. The presynaptic inhibitory terminal autoreceptors were first described for noradrenergic neurones (alpha 2-adrenoceptors) and subsequently for other neurotransmitters: dopamine (D2/D3), acetylcholine (M2), GABA (GABAB), histamine (H3) and serotonin (5-HT10). This negative feedback loop introduces terminal regulation into the neural secretory event. Saloman Langer describes how presynaptic terminal facilitatory receptors exist for the modulation of acetylcholine release and these autoreceptors are of the nicotinic subtype. Presynaptic release-modulating receptors represent targets for pharmacological intervention by exogenous compounds acting as agonists, partial agonists or antagonists. Compounds with such properties as the antidepressant mirtazepine (alpha 2-adrenoceptor antagonist) and the neuroleptic amisulpride (preferential presynaptic D2/D3 receptor antagonist) may represent the beginning of a new generation of innovative drugs with useful therapeutic properties.