ABSTRACT
Arousal is controlled via the complex interplay between a network of distinct wakefulness-and sleeppromoting nuclei in the brainstem and hypothalamus that release a variety of different neurotransmitters (Figure 27.1). The neurotransmitters used by the neurons in wakefulness-promoting nuclei include norepinephrine in the locus coeruleus (LC), histamine in the tuberomammillary nucleus (TMN), orexin/hypocretin in the lateral hypothalamic/perifornical area (LH/PF), serotonin (5-hydroxytryptamine, 5HT) in the dorsal raphe nuclei (DR), dopamine in the ventral tegmental area (VTA) and the periaqueductal gray (PAG), and acetylcholine in the laterodorsal tegmental nucleus (LDT), pedunculopontine tegmental nucleus (PPT), and the basal forebrain (BF). The neurotransmitters associated with sleep-promoting nuclei (BF and the ventrolateral preoptic area (VLPO) of the hypothalamus) are γ-aminobutyric acid (GABA) and galanin.1,2
The term ‘stimulant’ is a widely used but loosely defined term referring usually to drugs that produce generalized neuronal activation, resulting in increased alertness and reduced fatigue.3 However, recent research has shown that many drugs classed as ‘stimulants’ can interact with the arousal system in a localized and specific manner through the enhancement of the activity of wakefulness-promoting systems and/or through the inhibition of sleep-promoting systems. In this chapter, following a brief review of the current clinical use of stimulant drugs, the mechanism of action of currently available stimulant drugs will be considered together with pointers towards the development of novel clinically useful arousalenhancing agents.
